The Immune System in Cancer: If It Isn't Broken, Can We Fix It?

Terremovic, Dragan; Vile, Richard G.

doi:10.1002/3527600795.ch10

Cited by 1 publication

(1 citation statement)

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“…14 In this respect, we previously showed that by inducing "stressful death" of normal cells it was possible to generate autoimmune responses, which were also effective against tumor cells which share antigens with the normal tissue. [15][16][17][18][19][20] Therefore, we combined the concepts of inflammatory killing of normal cells to treat tumors, with the use of VSV as both an oncolytic and adjuvant. We hypothesized that, by expressing a cDNA library of a normal/tumor tissue from systemically delivered, immunogenic VSV, it would be possible to display a very broad repertoire of TAA, which are also expressed on tumors of the same histological type and against which T-cell responses would mediate tumor rejection.…”

Section: Introductionmentioning

confidence: 99%

The Profile of Tumor Antigens Which Can be Targeted by Immunotherapy Depends Upon the Tumor's Anatomical Site

et al. 2014

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Previously, we showed that vesicular stomatitis virus (VSV) engineered to express a cDNA library from human melanoma cells (ASMEL, Altered Self Melanoma Epitope Library) was an effective systemic therapy to treat subcutaneous (s.c.) murine B16 melanomas. Here, we show that intravenous treatment with the same ASMEL VSV-cDNA library was an effective treatment for established intra-cranial (i.c.) melanoma brain tumors. The optimal combination of antigens identified from the ASMEL which treated s.c. B16 tumors (VSV-N-RAS+VSV-CYTC-C+VSV-TYRP-1) was ineffective against i.c. B16 brain tumors. In contrast, combination of VSV-expressed antigens-VSV-HIF-2α+VSV-SOX-10+VSV-C-MYC+VSV-TYRP1-from ASMEL which was highly effective against i.c. B16 brain tumors, had no efficacy against the same tumors growing subcutaneously. Correspondingly, i.c. B16 tumors expressed a HIF-2α(Hi), SOX-10(Hi), c-myc(Hi), TYRP1, N-RAS(lo)Cytc(lo) antigen profile, which differed significantly from the HIF-2α(lo), SOX-10(lo), c-myc(lo), TYRP1, N-RAS(Hi)Cytc(Hi) phenotype of s.c. B16 tumors, and was imposed upon the tumor cells by CD11b(+) cells within the local brain tumor microenvironment. Combining T-cell costimulation with systemic VSV-cDNA treatment, long-term cures of mice with established i.c. tumors were achieved in about 75% of mice. Our data show that the anatomical location of a tumor profoundly affects the profile of antigens that it expresses.

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