B16 as a Mouse Model for Human Melanoma

Abstract

This unit details protocols for in vivo models of subcutaneous growth and pulmonary metastases of B16 melanoma. Therapeutic approaches include the use of B16.GM-CSF and rVVmTRP-1 to induce autoimmune vitiligo and tumor protection. The induction and use of gp 100-specific therapeutic cytotoxic T lymphocytes (CTL) are discussed. Methods are also included for CTL induction, isolation and testing, CTL maintenance, and adoptive transfer. Support protocols detail the testing of mouse sera for presence of MDA-specific antibodies by immunoblotting and ELISA, respectively. Additional sections, including growing B16 melanoma, enumerating pulmonary metastases, and use of recombinant viruses for vaccination, are discussed together with safety concerns.

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

“…In contrast, large B16F10 tumors, classically considered poorly immunogenic due to low MHC-I expression, 44 were only mildly affected by sequential therapy or monotherapy with poly(I:C) or R848. This suggests that for tumors with low mutational loads that lack neoantigens, or for tumors that are poorly T cell-inflamed, PRR-targeted therapy may need to be combined with other approaches targeting the T-cell repertoire, such as vaccination or checkpoint blockade 45 .…”

Anti-tumor activity mediated by protein and peptide transduction of HIV viral protein R (Vpr)

“…[55][56][57] In addition, very few other therapeutic strategies have proven to be successful in inducing regression of established tumors generated from B16.F10 cells. 58 These observations provided further experimental support for the potential utility of Vpr as an anti-cancer agent and the impetus for further analysis, by our group, of the biological activity of this protein.…”

Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor

“…We set out to study the immunologic aspects of the combination of adenovirus and adoptive T-cell therapy in a fully immunocompetent setting because tumor-infiltrating immune cells and components of stroma can have a major impact on the treatment outcome. For this, we used the B16 model, a highly immunosuppressive murine model of melanoma, which has been referred to as the ultimate preclinical test for immunotherapies (13). B16 cells expressing xenoantigen ovalbumin are generally considered immunogenic (based on tumor incidence rate after implantation and the induction of NK cells), but this model also exerts nonimmunogenic properties (very low expression of MHC class I, highly aggressive growth, and resistance to OT-I T cells).…”

“…We used the syngeneic C57BL/6 mouse B16.OVA melanoma tumor model, which is poorly immunogenic (13), and thus representative of advanced human melanomas (which are often initially immunogenic but then become severely immunosuppressive and immunoedited at the advanced metastatic stage). We observed superior antitumor efficacy and increased levels of tumor-infiltrating immune cells, enhanced maturation of APCs, and higher numbers of activated T cells in the combination-treated group compared with the group treated with T-cell therapy alone.…”