Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4733-4733 ◽  
Author(s):  
Valéria C.C. Andrade ◽  
André L. Vettore ◽  
Manuella S.S. Almeida ◽  
José S.R. Oliveira ◽  
Maria de Lourdes L.F. Chauffaille ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Prognostic Impact ◽  
Advanced Stage ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Three Samples ◽  
Cox's Regression ◽  
Ct Antigens ◽  
Cancer Testis

Abstract Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.

Frequency and Prognostic Relevance of Cancer Testis Antigen 45 Expression in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5134-5134
Author(s):  
Valeria C.C. Andrade ◽  
Gisele W. B. Colleoni ◽  
Andre Luiz Vettore ◽  
Maria R. R. Silva ◽  
Roberta Spetic Felix ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Line ◽  
Plasma Cell ◽  
Cell Morphology ◽  
Staging System ◽  
Monoclonal Gammopathies ◽  
Normal Tissues ◽  
Cancer Testis

Abstract Introduction: Cancer testis (CT) antigens have become the most extensively studied antigen group in the field of tumor immunology. CT45 antigen expression was described in colon adenocarcinomas, germ cell tumors, Hodgkin’s lymphomas and, more recently, in multiple myeloma (MM). Aims: This study aims to analyze the expression of CT45 in normal tissues and in plasma cell disorders and to identify possible associations with clinical data and prognosis in MM. Patients and Methods: The expression of CT45 was studied in twenty normal tissues (testis, placenta, skeletal muscle, bladder, lung, spleen, heart, brain, fetal brain, thymus, uterus, stomach, mammary gland, pancreas, prostate, small intestine, kidney, adrenal gland, spinal cord, colon and one pool of ten normal bone marrow samples) and in bone marrow aspirates from three monoclonal gammopathies of undetermined significance (MGUS), five solitary plasmacytomas, 61 newly diagnosed MM patients and MM cell line U266 by RT-PCR. Results: CT45 was positive in three out of 20 (15%) normal tissues tested: lung, brain (both fetal and adult) and spinal cord. Among monoclonal gammopathies, CT45 was positive in two out of five (40%) solitary plasmacytomas’ bone marrow aspirates, 10 out of 61 (16%) MM bone marrow aspirates and in the U266 MM cell line. Six out of 10 (60%) CT45 positive MM cases were classified as International Staging System (ISS) 3 (p = 0.009). Six CT45-positive cases were classified as plasmacytic (PC) and four as polymorphic (PM). Median OS of the MM group was 21 months. Nine patients were submitted to autologous stem cell transplantation. All of the transplanted cases were CT45-negative. Univariate analysis showed that Durie-Salmon Staging System (Durie-Salmon IIIA: N = 35, median OS = 40 months; Durie-Salmon IIIB: N = 19, median OS = 12 months; log-rank p= 0.0139), b2microglobulin (b2microglobulin £ 5.5 mg/L: N = 27, median OS = 40 months; b2microglobulin > 5.5 mg/L: N = 24, median OS = 12 months, log-rank p= 0.0520, Breslow p = 0.0352, Tarone-Ware p = 0.0399), plasma cell morphology (PC: N = 38, median OS = not reached; PM: N = 11, median OS = 12 months; PB: N = 5, median OS = 1 month; log-rank p= 0.0037), transplantation proceedings (transplanted patients: N = 9, median OS = not reached; non-transplanted patients: N = 47, median OS = 14 months; p = 0.0064) and CT45 expression (CT45 expression negative: N = 46, median OS = 25 months; CT45 expression positive: N = 10, median OS = 3 months, log-rank p = 0.038 for all patients and CT45 expression negative: N = 37, median OS = 19 months; CT45 expression positive: N = 10, median OS = 3 months, p = 0.0245, only non-transplanted patients) had impact on OS. Cox Regression Model showed that only plasma cell morphology (p = 0.029, RR 5.288, CI 1.77704–15.7988), transplant proceedings (p = 0.0742, RR 0.1582, CI 0.0209–1.1976) and CT45 expression (p = 0.0016, RR 7.0403, CI2.0978–23.6278) were independent prognostic factors in MM patients survival. CT45-positive cases were associated with poor outcome and presented 7 times more chance of worse evolution then the negative ones. Conclusions: CT45 was expressed in only 16% of MM patients. However, we demonstrated for the first time that positive expression of CT45 was associated with high ISS scores and poor outcome in MM

Frequent Expression of Cancer/Testis Antigens CT7 and LAGE-1 in Advanced Stage Multiple Myeloma: Are They Possible Targets for Immunotherapy?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5034-5034
Author(s):  
Valeria Cristina da Costa Andrade ◽  
Gisele Wally Braga Colleoni ◽  
Andre L. Vettore ◽  
Roberta Spetic Felix ◽  
Manuella S.S. Almeida ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Line ◽  
High Frequency ◽  
Positive Control ◽  
Proliferation Index ◽  
Advanced Stage ◽  
Normal Bone Marrow ◽  
Normal Tissues ◽  
Normal Bone

Abstract Introduction: Recently, Jungbluth and collaborators (Blood2005;106(1):167) demonstrated that CT7 and MAGE-A3/6 are frequently expressed in advanced stage MM patients and that higher levels of CT7 and MAGE-A3/6 proteins also correlate with elevated plasma-cell proliferation index. These findings suggest a possible pathogenic role of such proteins in MM and also show that they could be attractive targets for immunotherapy. Objectives: To analyze global expression of 13 CTs (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, MAGE-A10, MAGE-A12, BAGE-1, CT7, GAGE family, LAGE-1, PRAME, SP17 and SSX-1) in a panel of normal tissues and monoclonal gammopathies. Material and Method: We studied 13 normal tissues (skeletal muscle, bladder, lung, spleen, heart, brain, thymus, uterus, stomach, mammary gland, pancreas, prostate and colon, Clontech), six normal bone marrow aspirates (donors for allogeneic stem-cell transplants), one pool of 10 normal bone marrow samples (Clontech), three monoclonal gammophaties of undertermined significance (MGUS), five solitary plasmacytomas, 39 multiple myeloma samples (two Durie-Salmon stage II and 37 stage III) and MM cell line U266. Normal testis was used as positive control. Total RNA was extracted using Trizol reagent (Invitrogen). After cDNA synthesis, the expression of CTs was evaluated by RT-PCR and 2% agarose gel electrophoresis. Results: SP17 was positive in all seven normal bone marrow samples and in the 13 normal tissues tested. Thus, it was excluded from further analyses. CT7 was positive in one MGUS and in one plasmacytoma. U266 cell line was positive for all CTs, except SSX-1. The frequency of CTs expression in MM patients was: CT7 = 30/39 (77%); LAGE-1 = 18/39 (46%); MAGE-A3/6 = 16/39 (41%); MAGE-A2 = 14/39 (36%); GAGE family = 13/39 (33%); BAGE-1 = 11/39 (28%); MAGE-A1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGE-A12 = 8/39 (20,5%); MAGE-A4 and MAGE-A10 = 0%. It is important to note that from the 18 cases with less CT’s positivity (0, 1 or 2 positive-CTs), three were negative for all of them. Twelve of the remaining 15 cases (80%) were positive for CT7. We did not find association between International Scoring System and percentage of expressed CTs in 36 analyzed MM cases. Conclusion: Our results showed high frequency of expression of CT7 in advanced stage MM patients and support its importance as a target for immunotherapy, because it has a high incidence of positivity even in cases without expression of other CTs. As far we know, this is the second study showing high frequency (~ 50%) of LAGE-1 expression in MM (van Baren et al, 1999), also highlighting its importance as therapeutic target.

Immunohistochemical Detection of Cancer-Testis Antigen PRAME

2021 ◽  
pp. 106689692110120
Author(s):  
Cecilia Lezcano ◽  
Annette M. Müller ◽  
Denise Frosina ◽  
Enmily Hernandez ◽  
Jerica A. Geronimo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Molecular Data ◽  
Immunohistochemical Detection ◽  
Normal Tissues ◽  
Variable Extent ◽  
Formalin Fixed Paraffin Embedded ◽  
Myxoid Liposarcomas ◽  
Fetal Ovary ◽  
Ct Antigens ◽  
Cancer Testis

Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.

Expression of SSX-2 and SSX-4 Genes in Neuroblastoma

2002 ◽  
Vol 17 (4) ◽  
pp. 219-223 ◽  
Author(s):  
S.N. Chi ◽  
N.-K.V. Cheung ◽  
I.Y. Cheung
Keyword(s):  
Cytolytic T Lymphocytes ◽  
Rt Pcr ◽  
Normal Peripheral Blood ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Stage 4 ◽  
The Family ◽  
Prognostic Utility ◽  
Stage 1 ◽  
Cancer Testis

The SSX genes are members of the family of cancer/testis antigens that encode tumor-associated antigens recognizable by autologous cytolytic T lymphocytes. Their expression is common in tumors of diverse lineages and absent in normal tissues except testis and thyroid. In this study, sixty-seven neuroblastomas (NB) (12 stage 1, 13 stage 2, 12 stage 3, 12 stage 4S and 13 stage 4) were examined by RT-PCR and a sensitive chemiluminescent detection method for SSX-2 and SSX-4 expression. Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4. SSX-2 and SSX-4 positivity correlated with metastatic NB stage 4 (p=0.02 and p=0.006, respectively). Sensitivity experiments showed SSX-2 detection was one tumor cell in 106 normal cells, and one in 104 for SSX-4. All normal tissues (n=6), with the exception of testis, normal bone marrow (BM, n=12) and normal peripheral blood (PBL, n=10) were negative for SSX-2 and SSX-4 expression. Thirty-two BM and 14 PBL obtained from 35 stage 4 NB patients at 24 months from their diagnosis were evaluated for SSX-2 expression. Unlike another cancer/testis antigen, GAGE, only one BM sample was positive, and no prognostic utility could be established. Further investigation of SSX expression at other relevant time points is warranted.

scholarly journals Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5690
Author(s):  
Sharon Changshan Wu ◽  
Karl Münger
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Clinical Utility ◽  
Cancer Testis Antigens ◽  
Cancer Drivers ◽  
Ct Antigens ◽  
Almost All ◽  
Cancer Testis

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost all hallmarks of cancer, suggesting that they may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas. However, their role in the pathogenesis of these cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) mobilize specific therapeutic immunity for high-risk resected gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4535-4535 ◽  
Author(s):  
Qin Liu ◽  
Hanqing Qian ◽  
Jie Shao ◽  
Qiuping Xu ◽  
Huizi Sha ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Patients ◽  
Stage Iiib ◽  
Cell Responses ◽  
Cancer Testis Antigens ◽  
Ct Antigens ◽  
Gastric Cancer Patients ◽  
Cancer Testis

4535 Background: 35% of stage IIIB/C Gastric cancer patients will recurrent after D2 gastrectomy within one year. Mutation-derived epitopes (neoantigens) has been demonstrated to induce tumor cell specific immune responses controlling the tumor growth. Nanovaccine can increase antigen presentation efficiency and elicit potent antitumor T cell responses with robust therapeutic efficacy. We hypothesized that vaccination with neoantigens/cancer testis (CT) antigens could expand pre-existing and induce antigen-specific T-cells populations, favouring of tumor control enhancement. Here, we report the first-in-human application of this concept in gastric cancer. Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. PVAC is an amphiphiles nanovaccine loaded with multiple personalized neoantigens/cancer testis antigens designed to induce antigen specific T cells and associated antitumor responses. PVAC will be administrated to stage IIIB/IIIC gastric carcinoma after six cycles of adjuvant chemotherapy (S-1/Oxaliplatin or S-1/docetaxel). Each patient received PVAC by subcutaneous injection on Days 1, 4, 8, 15, 22, 43, 64, 85, 169, administrated with the adjuvant montanide ISA 51 VG. Safety, immunogenicity and clinical efficacy will be evaluated. Results: 25 stage IIIB or IIIC gastric cancer patients were enrolled in this study. Mean age was 54.3 years old (range: 34-70), and ECOG performance scores were 0 or 1. Repeated dosing has been well tolerated with mild local discomfort and no DLTs. Three patients were observed grade 2 local skin reactions in the injection sites. No SAEs related to PVAC have been observed. Among median follow up time of 12.6 months (range: 8.5-25.0 months), only two patients had local recurrence at 24.0 months and 10.5 months after surgery, respectivelt. The rest 23 patients remain disease free on study. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs. Conclusions: PVAC is a multiple neoantigen/CT antigens nanovaccine that personalizes tumor specific antigens and the individual patient’s capacity to respond. Addition of PVAC may prolong progression-free survival (PFS) after the standard of care chemotherapy. Clinical trial information: ChiCTR1800017319 .

scholarly journals Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Monireh Mohsenzadegan ◽  
Mahdieh Razmi ◽  
Somayeh Vafaei ◽  
Maryam Abolhasani ◽  
Zahra Madjd ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Histological Grade ◽  
Immunohistochemical Analysis ◽  
Tumor Aggressiveness ◽  
P Values ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Clinicopathological Significance ◽  
The Common ◽  
Cancer Testis

AbstractMelanoma antigen gene (MAGE)-A6 and MAGE-A11 are two of the most cancer-testis antigens overexpressed in various types of cancers. However, the clinical and prognosis value of MAGE-A6 and MAGE-A11 co-expression in the pathophysiology of the bladder is unknown. Three studies were selected from GEO databases in order to introduce the common genes that are involved in bladder cancer. Then immunohistochemical analysis for staining pattern and clinicopathological significance of suggested markers, MAGE-A6 and MAGE-A11, were performed in 199 and 213 paraffin-embedded bladder cancer with long adjacent normal tissues, respectively. A significant and positive correlation was found between both nuclear and cytoplasmic expressions of MAGE-A6 as well as expression of cytoplasmic MAGE-A11 with histological grade, PT stage, lamina propria invasion, and LP/ muscularis (L/M) involvement (all of the p-values in terms of H-score were < 0.0001). Additionally, significant differences were found between both nuclear and cytoplasmic MAGE-A6/MAGE-A11 phenotypes with tumor size (P = 0.007, P = 0.043, respectively), different histological grades, PT stage, LP involvement, and L/M involvement (all of the p-values for both phenotypes were < 0.0001). The current study added the value of these novel markers to the bladder cancer clinical settlement that might be considered as an admirable target for immunotherapy.

Treatment of Chronic Lymphocytic Leukemia with a Hypomethylating Agent Induces Expression of NXF2, An Immunogenic Cancer Testis Antigen

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4207-4207
Author(s):  
Jason A Dubovsky ◽  
Douglas G McNeel ◽  
John J. Powers ◽  
Eduardo M. Sotomayor ◽  
Javier Pinilla
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Antigen Presentation ◽  
Lymphocytic Leukemia ◽  
Active Immunotherapy ◽  
Aberrant Expression ◽  
Normal Tissues ◽  
Cancer Testis Antigens ◽  
Solid Malignancies ◽  
Specific Proteins ◽  
Cancer Testis

Abstract Critical to success of active immunotherapy against cancer is the identification of immunologically recognized cancer-specific proteins with low tolerogenic potential. Cancer testis antigens (CTAs) in particular, fulfill this requirement as a result of their aberrant expression restricted to cancer cells and lack of expression in normal tissues bypassing tolerogenic mechanisms against self. Although CTAs have been extensively studied in solid malignancies little is known regarding their expression in chronic lymphocytic leukemia (CLL). Using a two-pronged approach we evaluated the immunogenicity of 29 CTAs in 22 patients with CLL and correlated these results to RTPCR data from CLL cell lines and patient cells. We identified IgG specific antibodies for one antigen, NXF2 and confirmed this response by ELISA and Western blot. We found that treatment of CLL with 5-aza-2′-deoxycytidine can induce expression of NXF2 that lasted for several weeks after treatment. Treatment also increased levels of MHC and costimulatory molecules (CD80, CD86, and CD40) necessary for antigen presentation. In addition, we identified other promising antigens such as NY-ESO-1 and MAGE which may have potential immunotherapeutic application. Our findings suggest that NXF2 could be further pursued as an immunotherapeutic target in CLL, and that treatment with demethylating agents could be exploited to specifically modulate CTA expression and effective antigen presentation in malignant B-cells.

Expression of Cancer Testis (CT) Antigens NY-ESO-1 and LAGE-1 in Multiple Myeloma (MM): Could a Vaccine against the Former Antigen Be Effective against the Latter?

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4887-4887
Author(s):  
Bruno Karia ◽  
Fabricio de Carvalho ◽  
Valéria C.C. Andrade ◽  
Achim A. Jungbluth ◽  
André L. Vettore ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Expression ◽  
Cell Line ◽  
Mrna Level ◽  
High Similarity ◽  
Rt Pcr ◽  
Normal Tissues ◽  
U266 Cell ◽  
Ct Antigens ◽  
U266 Cell Line

Abstract Abstract 4887 Introduction In recent years, the expression of CT antigens has been studied in various malignant neoplasias. Based on their tumor-associated expression and due to their ability to elicit an immune response in the autologous host, CT antigens are potential targets for vaccine-based immunotherapy of cancer. Since different CT antigens can be expressed simultaneously in the same tumor, CT antigens are possible targets for polyvalent vaccines. Immunotherapy trials employing MAGE-A3 and NY-ESO-1 in MM patients are in progress. We previously reported frequent expression of LAGE-1 on mRNA level in MM patients (∼50%). Due to the high similarity between NY-ESO-1 and LAGE-1 (94% in mRNA and 84% in protein sequences) and the more prevalent presence of the latter, it is interesting to speculate if anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be efficient in patients with LAGE-1-positive tumors. Objectives To evaluate mRNA and protein expression of NY-ESO-1 and LAGE-1 in MM patients and to explore the possibility of an anti-NY-ESO-1 vaccine eliciting immunity to LAGE-1. Materials and methods The expression of NY-ESO-1 and LAGE-1 was studied by RT-PCR in 18 normal tissues, 28 bone marrow MM samples and U266 cell line. NY-ESO-1 and LAGE-1 protein expression were analyzed by immunohistochemistry in the MM specimens using monoclonal antibody (mAb) E978 and mAb 219-510-23 respectively. The protein extracts from U266 (NY-ESO-1+/LAGE-1+), H1299 (only NY-ESO-1+), SKBR3 (only LAGE-1+) and HaCat (double negative) cell lines were analyzed by Western Blot with mAb E978 (1:5,000). Results RT-PCR was positive for both genes in testis, placenta and U266 cell line. All other normal tissues were negative. In MM, LAGE-1 was positive in 36% (10/28) and NY-ESO-1 in 18% (5/28) of total bone marrow samples. However, only 2 patients (7%) were positive for protein expression by immunohistochemistry (both cases were also positive by RT-PCR). Both NY-ESO-1 mRNA-positive cell lines U266 and H1299 were positive by Western Blot for mAb E978, but this anti-NY-ESO-1 mAb was unable to identify LAGE-1 protein in U266 and SKBR3 cell line extracts. Conclusions In this small group of MM patients, NY-ESO-1 and LAGE-1 were expressed on mRNA level in 18% and 36% respectively, while both antigens were present on protein level in only 7%. Discrepancies between RNA and protein expression has been described in other tumors for CT antigens previously. The incidence of up to 36% LAGE-1 positive cases suggest that multiple myeloma might be susceptible to LAGE-1 and/or NY-ESO-1 vaccine-based immunotherapy. Also it is may be possible that, due to the high similarity between the proteins, anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be efficient in patients with LAGE-1-positive tumors. Disclosures No relevant conflicts of interest to declare.

Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1103-1112 ◽  
Author(s):  
Djordje Atanackovic ◽  
Julia Arfsten ◽  
Yanran Cao ◽  
Sacha Gnjatic ◽  
Frank Schnieders ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Immune Responses ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Antibody Responses ◽  
Ct Antigens ◽  
Cancer Testis

Abstract Immunotherapies using cancer-testis (CT) antigens as targets represent a potentially useful treatment in patients with multiple myeloma (MM) who commonly show recurrent disease following chemotherapy. We analyzed the expression of 11 CT antigens in bone marrow samples from patients with MM (n = 55) and healthy donors (n = 32) using reverse transcriptase–polymerase chain reaction (RT-PCR). CT antigens were frequently expressed in MM with 56% (MAGEC2), 55% (MAGEA3), 35% (SSX1), 20% (SSX4, SSX5), 16% (SSX2), 15% (BAGE), 7% (NY-ESO-1), and 6% (ADAM2, LIPI) expressing the given antigen. Importantly, CT antigens were not expressed in healthy bone marrow. Analyzing patients with MM (n = 66) for antibody responses against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT antigens preferentially in patients who had received allogeneic stem cell transplantation (alloSCT). Antibody responses against NY-ESO-1 correlated with NY-ESO-1–specific CD4+ and CD8+ T-cell responses against peptide NY-ESO-151-62 and CD4+ responses against NY-ESO-1121-140 in 1 of these patients. These allogeneic immune responses were not detectable in pretransplantation samples and in the patients' stem cell donors, indicating that CT antigens might indeed represent natural targets for graft-versus-myeloma effects. Immune responses induced by alloSCT could be boosted by active CT antigen–specific immunotherapy, which might help to achieve long-lasting remissions in patients with MM.

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