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Th1 epitopes as potential biomarkers for ipilimumab treatment

Date

09 Oct 2016

Session

Basic science and translational research

Presenters

Juan Marquez

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

J.P. Marquez1, E. Ramos2, D.R. Herendeen2, K. Quayle2, M.L. Verburg2, A. Suplee-Rivera2, S. Carrillo2, J.A. Matute-Briseno2, R. Soto-Soto2, A. Camacho-Hernandez2, P.A. Lucero-Diaz2

Author affiliations

  • 1 Oncology, Tumor Vaccine Group University of Washington, 98109-4714 - Seattle/US
  • 2 Immuno-oncology, CENTRO DE INVESTIGACION DEL CANCER EN SONORA, 85040 - Sonora/MX
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Background

Ipilimumab may unleash T cells in many tumors and effectively be combined with multi-antigen vaccines. The unleashed T cells could be detrimental if they are the wrong phenotype such as Th2. Th1 peptides from 4 proteins associated with bad prognosis were designed to assess the IFN-gamma production in presence and absence of ipilimumab. Then we prepared a pilot protocol with low dose of ipilimumab to treat patients suffering from several malignancies. We found that patients with pre-existing Th1 immune response from four overexpressed proteins had better clinical outcomes after treatment.

Methods

Naïve patients stage IV (n = 39) including ovarian (n = 10), triple negative breast cancer (TNBC; n = 8), multiple myeloma (MM; n = 5), colorectal (CRC; n = 10) and pancreatic cancer (n = 6) patients were studied. IFN-gamma and IL-10 ELISPOT assay was performed using 13 Th1 epitopes. Patients with predominant either Th1 (n = 11) and Th2 (n = 28) response were grouped and treated with 25-50 mg of total ipilimumab weekly for three weeks before starting standard of care treatment. Th1 epitopes from EGFR (4), Bcl-2 (3), Survivin (3) and Sox2 (3) were used for ELISPOT studies.

Results

Th1 peptide-specific immune responses against at least one Th1 epitope of each protein had better clinical responses with ipilimumab treatment in comparison with the Th2 patients (p = 0.001). Th1 responders pre-treated with ipilimumab before standard of care treatment had overall survival (OS) of 2 yrs for ovarian, 2.3 years for CRC, 1.8 years for MM, 2.6 years for TNBC and 8 months for pancreatic cancer. The Th2 responders had OS of less than 6 months in average.

Conclusions

Patients with pre-existing Th1 response had a better prognosis and better overall survival in comparison with Th2. This could explain why pseudoprogressions seen in patients treated with checkpoint inhibitors could be in fact progression disease due to the unleash of Th2 cells, which are associated in the majority of the tumors with bad prognosis and tumor progression. Antigen-specific immune response against Th1 epitopes from four bad prognosis proteins may serve as biomarker to treat multiple tumors with ipilimumab.

Clinical trial identification

DOES NOT APPLY

Legal entity responsible for the study

Centro De Investigacion Del Cancer En Sonora

Funding

Centro De Investigacion Del Cancer En Sonora

Disclosure

All authors have declared no conflicts of interest.

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