TMOD-14. CONJOINED CLASS I AND II EPITOPES ENHANCE NEOANTIGEN-TARGETED ACTIVE IMMUNOTHERAPY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi218-vi218
Author(s):  
Adam Swartz ◽  
Kendra Congdon ◽  
Smita Nair ◽  
Qi-Jing Li ◽  
James Herndon ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Response ◽  
Active Immunotherapy ◽  
Term Survival ◽  
Cell Responses ◽  
Helper Epitope ◽  
Single Antigen ◽  
Infiltrating Cells ◽  
Post Implantation

Abstract INTRODUCTION Cancer vaccines involve the administration of tumor-associated antigens into the host to generate anti-tumor T cell responses. Glioblastoma (GBM) is a disease with poor prognosis. GBM has a limited number of immunotherapeutic targets due to low mutational load, and is also highly heterogeneous; targeting a single antigen leads to antigen escape and tumor growth. METHODS VMDK mice were subcutaneously implanted with 750,000 SMA560 cells and on days 1 and 8 post implantation, mice were treated with 15 nmol of the universal helper epitope, P30, conjoined to the MHCI-restricted neoepitopes Odc1MHCI-P30 or Topbp1MHCI-P30. Human CD27 (hCD27) transgenic mice were intracranially implanted with CT2A-Odc1, followed by anti-CD27 and 15 nmol of Odc1MHCI-P30. B16.OVA or B16.F10 tumor cells were intracranially implanted in hCD27 mice and received SIINFEKL-P30 or Trp2-P30 conjoined peptides. Tumor growth, survival, or IFNγ secretion of splenic or tumor-infiltrating cells was assessed. RESULTS Unlike Odc1MHCI mixed with P30, conjoined Odc1MHCI-P30 had equivalent immunogenicity and anti-tumor efficacy to that observed with native long Odc1 peptide. Native long peptide of Topbp1 did not elicit an antitumor response, yet Topbp1MHCI-P30 caused an increase in numbers of IFNγ-secreting splenocytes and a decrease in tumor growth and similar to that seen with Odc1MHCI-P30 . Anti-CD27 treatment significantly increased numbers of IFNγ secreting splenocytes in Odc1MHCI-P30 vaccinated hCD27 mice, and the use of anti-CD27 with Odc1MHCI-P30 achieved long-term survival in 90% of tumor bearing hCD27 mice. Anti-CD27 synergized with SIINFEKL-P30 and Trp2-P30 to significantly improve survival after administration of these peptides. CONCLUSIONS Our work shows that poorly immunogenic neoantigens can be conjoined to P30 and used to generate an anti-tumor response in mouse models of GBM, and anti-tumor responses of conjoined peptides can be enhanced with anti-CD27 treatment. Together, these data demonstrate the efficacy of neoantigen vaccines for the treatment of heterogeneous GBM.

Long-Term Survival of a Patient with Hepatocellular Carcinoma under Treatment with Viscum album – Case Report

2021 ◽  
pp. 237-243
Author(s):  
Ana Catarina Viana Valle ◽  
Aloísio Cunha de Carvalho
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Liver Neoplasm ◽  
Viscum Album ◽  
Health Condition ◽  
Continuous Treatment ◽  
Term Survival ◽  
History Of ◽  
Application Frequency

Hepatocellular carcinoma (HCC) is the most common liver neoplasm in dogs and can be treated by the Viscum album therapy in a curative or palliative way. The objective is to report a hepatocellular carcinoma case in a dog treated by homeopathic therapy, extending to Palliative Care, with a 24-month survival. A 12-year-old Schnauzer male with a history of a liver nodule was treated by intravenous and subcutaneous applications of V. album in different dynamization and combinations, chromotherapy, and oral homeopathic medicines. The tumor growth was controlled, and the health condition of the patient was stable while the medication was given as prescribed. However, as application frequency was reduced, tumor growth increased, and health deterioration was verified. Nevertheless and contrary to expectations, the patient had a 24-month survival. Therefore, these findings point to the potential of V. album on enhancing the quality of life, controlling tumor growth, and prolonging survival on patients with HCC. Patients under continuous treatment would benefit better of these properties.

scholarly journals Long-term in vivo microscopy of CAR T cell dynamics during eradication of CNS lymphoma in mice

2019 ◽  
Vol 116 (48) ◽  
pp. 24275-24284 ◽  
Author(s):  
Matthias Mulazzani ◽  
Simon P. Fräßle ◽  
Iven von Mücke-Heim ◽  
Sigrid Langer ◽  
Xiaolan Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Therapeutic Effects ◽  
Term Survival ◽  
Car T Cells ◽  
Car T

T cells expressing anti-CD19 chimeric antigen receptors (CARs) demonstrate impressive efficacy in the treatment of systemic B cell malignancies, including B cell lymphoma. However, their effect on primary central nervous system lymphoma (PCNSL) is unknown. Additionally, the detailed cellular dynamics of CAR T cells during their antitumor reaction remain unclear, including their intratumoral infiltration depth, mobility, and persistence. Studying these processes in detail requires repeated intravital imaging of precisely defined tumor regions during weeks of tumor growth and regression. Here, we have combined a model of PCNSL with in vivo intracerebral 2-photon microscopy. Thereby, we were able to visualize intracranial PCNSL growth and therapeutic effects of CAR T cells longitudinally in the same animal over several weeks. Intravenous (i.v.) injection resulted in poor tumor infiltration of anti-CD19 CAR T cells and could not sufficiently control tumor growth. After intracerebral injection, however, anti-CD19 CAR T cells invaded deeply into the solid tumor, reduced tumor growth, and induced regression of PCNSL, which was associated with long-term survival. Intracerebral anti-CD19 CAR T cells entered the circulation and infiltrated distant, nondraining lymph nodes more efficiently than mock CAR T cells. After complete regression of tumors, anti-CD19 CAR T cells remained detectable intracranially and intravascularly for up to 159 d. Collectively, these results demonstrate the great potential of anti-CD19 CAR T cells for the treatment of PCNSL.

Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Hans-Rudolf Raab ◽  
Juergen Weitz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinical Trial Information

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]

Etoposide, cisplatin and doxorubicin in patients with small cell lung cancer: Tumor response and long term survival

1986 ◽  
Vol 22 (6) ◽  
pp. 701-708 ◽  
Author(s):  
Pierre Alberto ◽  
Bernadette Mermillod ◽  
Rudolf Joss ◽  
Jean Paul Obrecht ◽  
Georg Martz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Survival ◽  
Long Term Survival ◽  
Cancer Tumor

Disease control rate at 8 weeks as a predictive marker for long-term clinical outcomes in patients with advanced gastric cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 22-22
Author(s):  
Junho Yi ◽  
Gun Min Kim ◽  
Hyo Song Kim ◽  
Sun Young Rha ◽  
Hyun Cheol Chung
Keyword(s):  
Gastric Cancer ◽  
Disease Control ◽  
Early Phase ◽  
Tumor Response ◽  
Disease Control Rate ◽  
Powerful Predictor ◽  
First Line ◽  
Term Survival ◽  
Long Term Survival

22 Background: Survival is the ultimate end-point in field of medical oncology. Although tumor response has been used as surrogate end-point in early phase clinical trial in patients with gastric cancer, clear correlation between tumor response and long-term survival has not been established yet. The objective of the current study is to determine whether early assessment could predict survival in patients with AGC. Methods: A total of 337 patients with AGC who had participated one of the three first-line, prospective, investigator-initiated, randomized trials carried out in Yonsei Cancer Center were included in the analysis. 238 had received fluoropyrimidine (F) + platinum (P), 61 had received F + taxane (T), 38 had received T + P. Response was assessed according to RECIST 1.1 at 8, 14 and 20 weeks after initiation of treatment. The correlation between response at each time point and the OS was evaluated using logistic regression test. Results: The median OS was 13.7 months. (95% CI 11.8 – 15.6) In terms of confirmed tumor response, 1 CR, 84 PRs, 104 SDs and 148 PDs were observed. At every landmark period, disease control rate (DCR, CR + PR + SD) was superior in predicting OS comparing with response rate. (RR, CR + PR) (Table). Among them, 8-week DCR was the most powerful predictor for OS. (HR 0.18, p< .001) There was no significant OS difference between patients with (13.7 months) vs. without (13.9 months) measurable lesions (p = .705) and between patients with 8-week response of PR (18.1 months) vs. SD (15.3 months) (p = .522). Conclusions: Disease control was a better predictor for OS in patients with AGC who had received first-line chemotherapy than response, with disease control at 8 week being the most powerful predictor. This could be used as a surrogate marker for long-term survival in early phase clinical trials. [Table: see text]

scholarly journals BAFFR controls early memory B cell responses but is dispensable for germinal center function

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Angelica W.Y. Lau ◽  
Vivian M. Turner ◽  
Katherine Bourne ◽  
Jana R. Hermes ◽  
Tyani D. Chan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Memory B Cells ◽  
Term Survival ◽  
Cell Responses ◽  
Tnf Superfamily ◽  
Surface Receptor ◽  
Early Memory

The TNF superfamily ligand BAFF maintains the survival of naive B cells by signaling through its surface receptor, BAFFR. Activated B cells maintain expression of BAFFR after they differentiate into germinal center (GC) or memory B cells (MBCs). However, the functions of BAFFR in these antigen-experienced B cell populations remain unclear. Here, we show that B cell–intrinsic BAFFR does not play a significant role in the survival or function of GC B cells or in the generation of the somatically mutated MBCs derived from them. Instead, BAFF/BAFFR signaling was required to generate the unmutated, GC-independent MBCs that differentiate directly from activated B cell blasts early in the response. Furthermore, amplification of BAFFR signaling in responding B cells did not affect GCs or the generation of GC-derived MBCs but greatly expanded the GC-independent MBC response. Although BAFF/BAFFR signaling specifically controlled the formation of the GC-independent MBC response, both types of MBCs required input from this pathway for optimal long-term survival.

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