Background: In a first in men, proof-of-principle, multi-center, open-label, single-arm, non-randomized phase 1/2 clinical ASET trial (ClinicalTrials.gov: NCT01265368; EudraCT No.: 2009-016853-16) in patients with advanced RCC the tumor vaccine MGN1601 has shown a good safety profile and improved overall survival in the per-protocol (PP) treated patient population. MGN1601 is a cell-based tumor vaccine consisting of two active pharmaceutical ingredients: Allogeneic (human) cells originating from renal cell carcinoma were gene-modified with four different MIDGE vectors encoding IL-7, GM-CSF, CD80 and CD154. These vaccine cells were combined with the synthetic DNA-based immunomodulator dSLIM®, a potent TLR-9 agonist.
Methods: The tumor vaccine MGN1601 – each dose consists of 107 vaccine cells and 5 mg dSLIM® – was administered 8 times over 12 weeks with 3 weekly and 5 bi-weekly administrations (PP population) in the ASET trial. Specific humoral immune responses in sera from patients before and after treatment with MGN1601 against a natural set of 17 known tumor associated antigens (TAA) expressed by the vaccine cells were evaluated ex-vivo in a translational research program using peptide arrays. On the array each TAA was represented by peptides of 15 amino acids length with an overlap of 13 amino acids.
Results: Nineteen heavily pre-treated patients with advanced RCC have been included into the trial. In the PP population – comprising 10 of these 19 patients – the humoral immune response against TAA expressed on vaccine cells was evaluated. Within each antigen subsets of overlapping peptides were recognized by patient's sera with an abundant or clearly increased intensity after MGN1601 treatment indicating favoured immunogenic regions within a TAA for an individual immune response. Such sets of peptides were identified within each antigen showing individual responses by sera from 2 to eight patients. Remarkably, some of these overlapping peptides were recognized by sera of more than one patient (“shared immunogenic regions”): In particular, 50 to 70 % of treated patients shared response to immunogenic regions within Survivin, Stromelysin, c-Myc, Histone H1.2 and G1/S-specific Cyclin-D1 indicating their comprehensive immunogenic potential. Within other TAA (e.g. p53, telomerase) shared immune responses to peptides were observed at lower rates (20 to 40% of patients), whereas for some of the antigens (e.g. MUC1, Her2/neu) only individual immune responses to the peptides were identified.
Conclusions: The humoral immune response – assessed in patients treated with the tumor vaccine MGN1601 – revealed overlapping peptides within various TAA that induced an immune response shared by up to 7 of 10 patients, indicating comprehensive immunogenic regions within those TAA and their potential use as vaccine epitopes. The specific evaluation of immune response to those TAA remains to further studies.
Citation Format: Manuel Schmidt, Barbara Volz, Kerstin Kapp, Viktor Gruenwald, Matthias Schroff, Burghardt Wittig. Immune responses against tumor associated antigens are induced by treatment with the cell-based tumor vaccine MGN1601 in patients with renal cell carcinoma. [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 A034.
- ©2016 American Association for Cancer Research.