Immunotherapy has emerged as one of the most efficacious form of cancer therapy. We have previously demonstrated MAGED4B short peptides are efficacious in inducing patients' immune responses in vitro. However, effective vaccination against tumours requires generation of both CD8+ and CD4+ T-cell responses. A critical role of CD4+ helper T cells in the development of CD8+ tumour-specific effector function has been shown by numerous studies. In this pilot study, we aim to compare the efficacy of MAGED4B specific-short peptides (SP), long peptide (LP) and the combination of both short and long peptides in inducing patients' immune responses in vitro. Briefly, peripheral blood mononuclear cells (PBMC) from HLA-A2 positive healthy volunteers were incubated with 10 μg/ml of peptide in the presence of IL-2 and IL-7 for 7 days; peptide exposed PBMC were then incubated with cancer cells expressing MAGED4B overnight. Capability of T cells to secrete IFN-γ was accessed using ELISPOT assay and CEF peptides pool was used as positive control. Our data demonstrated that all MAGED4B peptides (short and long) are capable to induce similar and/or higher cytokine secretion compared to CEF peptides pool suggesting that these peptides are highly immunogenic. MAGED4B specific SP are better in inducing cytolytic activity compared to MAGED4B specific LP; however when both LP and SP were mixed as a cocktail, we observed a reduction in cytokine secreting T cells when the immune cells were co-incubated with MAGED4B expressing cell line, advocating an inhibition instead of synergizing reaction. In summary, our data has corroborated our previous finding that HLA-A2 restricted MAGED4B specific SP are immunogenic. However, we did not observed a synergistic event when SP and LP were used in a cocktail, questioning the combinatorial effect of CD4+ and CD8+ T cells. These preliminary findings would need to be validated in a bigger cohort of patients.
Citation Format: Kue Peng Lim, Ai Leng Chun, Sathibalan Ponniah, Sok Ching Cheong. MAGED4B specific peptides: Short or long or combination? [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A158.
- ©2016 American Association for Cancer Research.