Generation of functional canine TIL products for solid tumors

Area of Science:

• Comparative oncology
• Immunotherapy
• Cellular therapy

Background:

• Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) is effective for human metastatic melanoma.
• Challenges remain for low tumor mutational burden (TMB) cancers.
• Murine models for preclinical evaluation have limitations in reflecting human tumor-immune interactions.

Purpose of the Study:

• To explore the potential of canine cancer patients with naturally occurring low TMB malignancies as a parallel model for TIL therapy.
• To establish protocols for expanding TILs from canine tumors.
• To assess the feasibility and functionality of canine TILs for adoptive cell therapy.

Main Methods:

• Developed protocols for expanding TILs from canine oral melanoma and appendicular osteosarcoma.
• Assessed TIL expansion despite low T cell frequencies in tumor digests.
• Evaluated TIL reactivity against autologous tumor cells and MHC class I dependency using beta-2-microglobulin (B2M)-ablated samples.

Main Results:

• Successfully developed protocols to expand TILs from canine oral melanoma and osteosarcoma.
• A subset of canine TIL products demonstrated reactivity to autologous tumor cells.
• TIL recognition was confirmed to be major histocompatibility complex (MHC) class I-dependent.

Conclusions:

• Generating functional canine TIL products is feasible.
• Canine cancer patients offer a valuable immunocompetent model for TIL therapy research.
• These findings pave the way for comparative trials evaluating TIL efficacy in low-TMB malignancies.