P03.03 Active immunization against human endogenous retrovirus type K (HERV-K) as an immunotherapeutic strategy against solid tumors

Abstract

databases), combined with the novel adjuvant CAF09b and used for the immunisation of HHDII/DR1 and HHDII/DP4 mice. Following splenocyte extraction, peptides-derived vaccines were tested for immunogenicity using IFNg ELISpot assays and killing of target cells was assessed using the same assay, co-culturing isolated CD3 + T cells with antigen-expressing cancer cells. Results Antigen expression of TNBC cell lines as revealed by qPCR suggested that treatment with 5mM DAC induced optimal upregulation, with 10mM usually leading to a plateau. These observations were confirmed by western blotting. Splenocytes derived from CAF09b-adjuvanted NY-ESO-1/HAGE/ WT1 vaccine-immunised mice showed strong IFNgresponses, and the isolated CD3 + T cells from these splenocytes could specifically recognise TNBC cells expressing all three antigens in a HLA-A2 restricted manner. Conclusions We propose the use of mutated NY-ESO-1/HAGE/ WT1-derived peptides in combination with CAF09b for the treatment of GBM, PCa and TNBC at a stage where no tumour cells can be detected to prevent or delay relapse in these malignancies.

Anti-HERV-K Drugs and Vaccines, Possible Therapies against Tumors

“…MVA-HK con vaccine [157] Gag [157] Inducing the T cell immune responses, knocking out the cells positive to HERV-K [157] Suppressing growth of the tumor and reducing pulmonary metastases [157] Active immunization via engineered adenovirus type 5 and 19a/64 carrying ISD-mutant HERV-K Gag and Env [158] Gag and Env [158] Rapid antibody T cell responses in mice, immune tolerance breakdown in non-human primates [158] Suppressing growth of tumors [158] Anti-HERV-K Env monoclonal antibodies [144] Env [144] mAbs 1 Env and T cell immune response in breast cancer, high number of cell surface molecules in human breast cancer that target the B cell response [144] mAbs: generally restrained development of cancerous cells and promoted apoptosis of them in in vitro conditions [144]. 6H5 mAb: diminished expansion of xenograft tumors due to its cytotoxic profile [159].…”

“…Antibody-Based Therapies 3.2.1. Active Immunization against HERV-K as a Therapy against Solid Tumors Human adenoviruses could be exploited in immunotherapy against solid tumors in order to carry HERV-K immunogens [158]. Earlier, a study depicted that an endogenous variant of murine leukemia that was transfected into adenoviral vectors could heal smalldimension cancers.…”

“…Earlier, a study depicted that an endogenous variant of murine leukemia that was transfected into adenoviral vectors could heal smalldimension cancers. In a recent investigation, engineered adenoviruses type 5 and 19a/64 that carried HERV-K Gag and Env genes underwent mutations in immunosuppressive domains (ISD) of Env glycoproteins [158]. Then, expression of HERV-K Gag and Env were evaluated in both human and murine DCs, followed by testing subsequent immunogenicity through intracellular cytokine staining and tetramers analyses [158].…”

“…In a recent investigation, engineered adenoviruses type 5 and 19a/64 that carried HERV-K Gag and Env genes underwent mutations in immunosuppressive domains (ISD) of Env glycoproteins [158]. Then, expression of HERV-K Gag and Env were evaluated in both human and murine DCs, followed by testing subsequent immunogenicity through intracellular cytokine staining and tetramers analyses [158]. At the next level, HERV-K-excited immune cells were collected from immunized mice and transferred to tumor-bearing mice (their murine colorectal cancer cells were genetically engineered to express the HERV-K Gag and Env antigens) [158].…”

“…Then, expression of HERV-K Gag and Env were evaluated in both human and murine DCs, followed by testing subsequent immunogenicity through intracellular cytokine staining and tetramers analyses [158]. At the next level, HERV-K-excited immune cells were collected from immunized mice and transferred to tumor-bearing mice (their murine colorectal cancer cells were genetically engineered to express the HERV-K Gag and Env antigens) [158]. Moreover, transfer of ISD-mutagenic HERV-K Gag and Env (HERV-K-ISDmut) via adenoviral carriers enhanced not only expression of HERV-K but also immune responses, including rapid antibody T cell responses in mice and immune tolerance breakdown in non-human primates [158].…”