scholarly journals Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen-4

2005 ◽  
Vol 23 (25) ◽  
pp. 6043-6053 ◽  
Author(s):  
Peter Attia ◽  
Giao Q. Phan ◽  
Ajay V. Maker ◽  
Michael R. Robinson ◽  
Martha M. Quezado ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Response Rate ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Regression ◽  
Objective Response ◽  
Prior History ◽  
Human Antibody ◽  
Peptide Vaccination ◽  
Lymphocyte Antigen

Purpose Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti–CTLA-4 and to explore the relationship between autoimmunity and tumor regression. Patients and Methods A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status ≥ 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti–CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). Results Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules. Conclusion Administration of anti–CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors

2016 ◽  
Vol 23 (8) ◽  
pp. 620-624 ◽  
Author(s):  
Belal Firwana ◽  
Rahul Ravilla ◽  
Mihir Raval ◽  
Laura Hutchins ◽  
Fade Mahmoud
Keyword(s):  
Cell Death ◽  
Adverse Event ◽  
T Cell ◽  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Stage Iii ◽  
Lymphocyte Antigen

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.

scholarly journals Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma

2020 ◽  
Vol 8 (2) ◽  
pp. e000627 ◽  
Author(s):  
Celine Boutros ◽  
Nathalie Chaput-Gras ◽  
Emilie Lanoy ◽  
Alicia Larive ◽  
Christine Mateus ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Dose Escalation ◽  
Clinical Benefit ◽  
Cytotoxic T Lymphocyte ◽  
Phase 1 ◽  
Objective Response ◽  
Severe Toxicity ◽  
Phase 1 Study

BackgroundA synergy between radiotherapy and anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA-4) monoclonal antibody has been demonstrated preclinically. The Mel-Ipi-Rx phase 1 study aimed to determine the maximum tolerated dose (MTD) and safety profile of radiotherapy combined with ipilimumab in patients with metastatic melanoma.Patients and methodsA 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of radiotherapy at week 4 combined with 10 mg/kg ipilimumab every 3 weeks for four doses. Patients with evidence of clinical benefit at week 12 were eligible for maintenance with ipilimumab 10 mg/kg every 12 weeks starting at week 24 until severe toxicity or disease progression. The database lock occurred on April 30, 2019. Tumor growth rate of irradiated lesions and non-irradiated lesions were analyzed to assess the systemic immunologic antitumor response. Blood immune monitoring was performed before and during treatment to determine if radiotherapy could modify ipilimumab pharmacodynamics.Results19 patients received ipilimumab between August 2011 and July 2015. Nine patients received the four doses of ipilimumab. All patients received the combined radiotherapy. Grade 3 adverse events occurred in nine patients, the most common being colitis and hepatitis. No drug-related death occurred. Dose limiting toxicity occurred in two of six patients in the cohort receiving 15 Gy. The MTD was 9 Gy. Two patients had complete response, three had partial response response and seven had stable disease, giving an objective response rate of 31% and a clinical benefit rate of 75% at week 24. The median duration of follow-up was 5.8 years (Q1=4.5; Q3=6.8). The median overall survival (95% CI) was estimated at 0.9 years (0.5–2). The median progression-free survival (PFS) (95% CI) was 0.4 (0.2–1.4). Radiotherapy combined with ipilimumab was associated with increased CD4+ and CD8+ICOS+ T cells. Increased CD8+ was significantly associated with PFS.ConclusionWhen combined with ipilimumab at 10 mg/kg, the MTD of radiotherapy was 9 Gy. This combination of ipilimumab and radiotherapy appears to be associated with antitumor activity. Increased CD8+ was significantly associated with PFS. Thus, immune biomarkers may be useful for early response evaluation.Trial registration numberNCT01557114.

scholarly journals Expression of FOXA1 Is Associated with the Tumor-Infiltrating M2 Macrophage, Cytotoxic T Lymphocyte, and Effect of Chemotherapy in Bladder Cancer

2021 ◽  
pp. 1-6
Author(s):  
Yiduo Wang ◽  
Huan Qu ◽  
Bin Xu ◽  
Jianping Wu ◽  
Kai Lu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Clinical Response ◽  
T Lymphocyte ◽  
Objective Response Rate ◽  
Immune Cell ◽  
Response Rate ◽  
Cytotoxic T Lymphocyte ◽  
Objective Response ◽  
Immune Cell Infiltration ◽  
Foxa1 Expression

Purpose: Cisplatin-containing combination chemotherapy has been the standard of care since the late 1980s, but the response rate is <50%. Studies have shown that the efficiency of chemotherapy differs among molecular subtypes of bladder cancer. In this study, we aimed to correlate FOXA1, a marker for differentiation of the basal and luminal subtypes, with tumor immune cell infiltration and the effect of chemotherapy in bladder cancer. Materials and Methods: Eighty-three patients with bladder cancer treated with chemotherapy were reviewed. Clinicopathological variables for each case were recorded. FOXA1, M2 tumor-associated macrophage (TAM), dendritic cell (DC), and cytotoxic T lymphocyte (CTL) were examined by immunohistochemistry. The relationship between FOXA1, immune cell infiltration, and clinical response to chemotherapy was assessed. Results: The overall objective response rate was 34%. The objective response rate for tumors with lower FOXA1 expression was 58% and for tumors with higher FOXA1 expression was 12%. Tumors with infiltrated M2 TAM proportion <3% had a higher objective response rate compared with infiltrated M2 TAM proportion >3% tumors (46% vs. 21%, p = 0.02). Tumors with infiltrated CTL proportion >5% had a higher objective response rate compared with infiltrated CTL proportion <5% tumors (50% vs. 17%, p = 0.002). DCs showed no significant differences. We found that the objective response rate for tumors with lower FOXA1 expression, proportion <3% M2 TAM infiltration, and proportion >5% CTL infiltration is 82%. Lower FOXA1 expression was associated with low M2 TAM infiltration and high CTL infiltration. Conclusions: Thus, we showed that in patients with bladder cancer who received chemotherapy, the higher clinical response rate is associated with low FOXA1 expression, low M2 TAM infiltration, and high CTL infiltration.

Sustained clinico-radiologic response to anti-cytotoxic T lymphocyte antigen 4 antibody therapy in metastatic myxoid liposarcoma

2016 ◽  
Vol 23 (7) ◽  
pp. 549-551
Author(s):  
Constantin A Dasanu
Keyword(s):  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Antibody Therapy ◽  
Myxoid Liposarcoma ◽  
Effective Control ◽  
Lymphocyte Antigen

Rarity and heterogeneity of sarcomas pose significant challenges in terms of developing new therapies. Therefore, efforts towards studying immunotherapy in sarcomas may provide hope for effective control of this group of devastating cancers. A sustained clinico-radiologic response to the anti-cytotoxic T lymphocyte antigen 4 antibody ipilimumab in a patient with metastatic myxoid liposarcoma is reported. Although the patient was treated with this agent for metastatic melanoma, both his metastatic cancers – melanoma and sarcoma – meaningfully responded to this agent. Consideration of enrolling patients in immunotherapy trials using various immune checkpoint inhibitors, where available, is of paramount importance, especially when facing advanced and/or refractory sarcoma situation.

Cytotoxic T-lymphocyte antigen-4 haplotypes and T cell activation in irritable bowel syndrome

2007 ◽  
Vol 45 (08) ◽  
Author(s):  
T Liebregts ◽  
B Adam ◽  
C Bredack ◽  
S Lester ◽  
S Downie-Doyle ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen ◽  
Irritable Bowel

Cytotoxic T lymphocyte antigen 4 polymorphisms and allergic asthma

2004 ◽  
Vol 34 (1) ◽  
pp. 4-8 ◽  
Author(s):  
A. J. M. Van oosterhout ◽  
D. T. Deurloo ◽  
P. C. Groot
Keyword(s):  
Allergic Asthma ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen

Markers for Anti-cytotoxic T-lymphocyte Antigen 4 (CTLA-4) Therapy in Melanoma

2013 ◽  
pp. 83-95 ◽  
Author(s):  
Michael A. Postow ◽  
Jianda Yuan ◽  
Shigehisa Kitano ◽  
Alexander M. Lesokhin ◽  
Jedd D. Wolchok
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen
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