Journal of Vaccines & Vaccination

Cancer Peptide Vaccine Therapy: Improving Anti-Tumor Effects

Meka Pavan Kalyan^* Department of Pharmacy, Avanthi Institute of Pharmaceutical Sciences, Cherukupally, India
^*Correspondence: Meka Pavan Kalyan, Department of Pharmacy, Avanthi Institute of Pharmaceutical Sciences, Cherukupally, India, Email:

Received: 06-Dec-2021 Published: 27-Dec-2021

Description

Cancer peptide vaccination therapies are predicted to prevent or minimize recurrences while prolonging lives and maintaining patient Quality Of Life (QOL). Glypican-3 (GPC3) is a cancerspecific antigen, as we previously described. GPC3-derived peptides have been found to be capable of activating peptidespecific Cytotoxic T cells, according to research (CTLs). In Hepatocellular Carcinoma, several clinical trials using the GPC3 peptide vaccination treatment has been conducted (HCC). Previous research has established the vaccine's safety and immunological efficacy, as well as its ability to induce therapeutic effects in some individuals. The clinical efficacy of cancer peptide vaccination treatments, however, is currently seem to be insufficient. As a result, we've tried to come up with viable ways to improve peptide vaccination therapy.

Antigen-specific CTLs identify antigen-derived peptides bound to Major Histocompatibility Complex (MHC) class I molecules on the tumour cell surface and kill the tumour cells in antigenspecific cancer immunotherapy. One of the reasons why antigenspecific cancer immunotherapy has been ineffective in clinical trials is the low density of delivered antigen associated to MHC class I molecules. We found that most cancers had increased expression of the Human Leukocyte Antigen (HLA) class I molecules, and that this expression was higher within the tumour area than outside it. To successfully enhance the antitumor efficacy of peptide vaccines, we used Intratumoral peptide injection to induce increased peptide onto MHC class I molecules present on tumour cells.

Intratumoral peptide injections were found to be helpful in slowing tumour growth and extending survival time. Furthermore, the peptide injection had an antigen spreading effect, which increased tumour cell antigenicity and could be a useful tool for increasing the anti-tumor effects of antigenspecific cancer immunotherapy against solid tumours. PD-1 is a protein that induces inhibitory signals in activated T and B lymphocytes. The PD-1/PDL1 pathway has been implicated with impaired tumour immunity in several studies. In both animal and clinical settings, we have induced peptide vaccines emulsified with Incomplete Freund's Adjuvant (IFA). The antigen-driven expression of the inhibitory receptors PD-1, LAG-3, CTLA-4, and Tim-3 in CTLs was enhanced after peptide/IFA immunisation. PD-1 blockade could partially rescue CTLs in a state of exhaustion. Therefore we employed the combination therapy by using the peptide vaccine and PD-1 blocking antibody. We demonstrated that PD-1/PD-L1 blockade enhanced the anti-tumor effects of peptide vaccines by increasing the immune response of vaccine-induced CTLs.

CTLs in a condition of depletion could benefit from PD-1 blockage. As a result, we used a combination therapy that included a peptide vaccination and a PD-1 blocking antibody. We found that blocking PD-1/PD-L1 increased the immunological response of vaccine-induced CTLs, which improved the anti-tumor effects of peptide vaccines. Several studies have demonstrated that depleting CD⁴⁺ cells enhances CTL responses, resulting in potent anti-tumor effects in tumorbearing mouse models. We used an anti-CD4 monoclonal Antibody (mAb) in a mouse model to boost the anti-tumor effects of peptide vaccinations. The number of ovalbumin (29)- specific CTLs induced by OVA peptide vaccine in combination with anti-CD4 mAb was larger than that inducted by OVA peptide vaccine alone, according to the IFN— ELISPOT assay. Furthermore, when CD107^a+cells were given a combination of OVA peptide vaccination and anti-CD4 mAb, perforin and granzyme secretion increased, as did the generation of IL-2 and TNF from these CTLs, as measured by the CD107a assay and the cytokine assay, respectively. Finally, in a mouse model of liver metastasis, the peptide vaccine in conjunction with anti-CD4 mAb inhibited metastases significantly.

The liver metastasis mouse model was created by introducing tumour cells into the spleen. Because the number of metastases in the mouse liver could not be quantified, the weight of the murine liver was used to assess hepatic metastasis. The liver weight of the OVA peptide vaccine and anti-CD4 mAb combination group was significantly lower than the untreated group and the OVA peptide vaccine alone group. The liver weight of the combination group, on the other hand, did not differ significantly from that of the anti-CD4 mAb alone-treated group. The improved inhibitory effects on metastasis in combination therapy, according to the IFN-ELISPOT assay, CD107a upregulation assay, and cytokine assay, were generated from an increase in the multi-functionality of peptide-specific CTLs. In order to assess liver metastasis based on the number of metastases, more research is needed.

Peptide vaccines have several drawbacks, such as poor anticancer effects, but they also offer some benefits, such as systemic effects equivalent to chemotherapies with fewer side effects. Intratumoral peptide injection or combination therapies with antibody medicines, for example, can improve the anti-tumor impact of cancer peptide vaccination therapy.