A universal anti‐cancer vaccine: Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival

Abstract

For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor-associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen. These DCs are then delivered to the host and elicit an immune response against the antigen of interest. We have recently established an mRNA genetic platform which induced specific CD8 cytotoxic T cell response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs vaccine platform was developed to activate CD4 T cells and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHC-II binding peptide sequences of melanoma antigens. These chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor specific CD4 T cells. When administered in combination with the MHC-I platform into tumor bearing mice, these constructs were able to inhibit tumor growth, and improve mouse survival. Deciphering the immunological mechanism of action, we observed an efficient CTLs killing in addition to higher levels of Th1 and Th2 subsets in the groups immunized with a combination of the MHC-I and MHC-II constructs. These universal constructs can be applied in multiple combinations and offer an attractive opportunity to improve cancer treatment.

Lenalidomide Augments the Antitumor Activities of Eps8 Peptide-Specific Cytotoxic T Lymphocytes against Multiple Myeloma

“…Among several types of cancer immunotherapies, peptide vaccines are one of the most successful public health interventions, preventing and controlling tumor progression in an efficient and cost-effective manner. It is essential that more suitable and immunogenic TAAs should be chosen for the induction of more robust antitumor immune responses using multiplepeptide cocktail vaccines (26). Here, we focused on the HLA-A Ã 0201 allele as it is the most common HLA class I subtype in the Caucasian population (27).…”

On the development of a neoantigen vaccine for the prevention of Lynch Syndrome

“…This in vivo CTL assay was previously described by our lab 21 . Two weeks following the final BMDC immunization, mice were injected intravenously (IV) with 20×10 6 target cells consisting of splenocytes from B6.SJL (CD45.1) mice loaded with peptides (30 μg/mL of Sp6D1, SIINFEKL or DMSO) and labeled with CFSE (eBioscience) using various concentrations at a 1:1:1 ratio (3, 0.3 and 0.03 μM, respectively).…”

The use of RNA-based treatments in the field of cancer immunotherapy

“…The use of DCs in cancer immunotherapy made sense because of their pivotal function in initiating antigenspecific immune responses [233]. Some researchers described how DCs electroporated with mRNA might trigger strong immune responses against tumor antigens [234]. Stimulating DCs with ovalbumin (OVA)-encoding mRNA or tumor-derived RNAs dampened the immune response in OVA-expressing and other mice models of melanoma [235].…”