Is immunotherapy the key to wiping out canine cancer?

Clinical evidence of the immune system's ability to control cancer comes from a number of observations in both the veterinary and medical settings. Consider the following examples:

• Cats receiving chronic immunosuppression following renal transplant have a higher incidence of lymphoma compared with the general feline population^1,2
• Spontaneous regression of transmissible venereal tumor is associated with an increased proportion of tumor-infiltrating cytotoxic CD8+ T cells³
• Canine osteosarcoma patients that develop bacterial infections after limb-sparing surgery experience significantly prolonged survival times.⁴ The presence of tumor-specific, cytotoxic T cells within tumors, such as ovarian carcinoma, confers a favorable prognosis,⁵ whereas infiltration with regulatory or suppressor T cells confers a worse prognosis⁶

These observations, coupled with two decades of experimentation in murine cancer models, indicate that finding ways to initiate, augment, and broaden a patient's antitumor immune response holds promise for the treatment and possible prevention of cancer. Indeed, this is the aim of cancer immunotherapy, and recent advances in this field have delivered unprecedented clinical results, including the induction and maintenance of durable remissions in patients with relapsed, refractory hematological and solid tumors, such as malignant melanoma. Together, this raises hope immunotherapy treatment regimens will one day lead to a cure.

Chimeric antigen receptor T cells
The term "cancer immunotherapy" applies to any approach aiming to promote effective antitumor immunity. One of the most promising proposed treatments to date has been the use of adoptive cell therapy (ACT) using chimeric antigen receptor (CAR) T cells. CAR-T cells are autologous T cells that are genetically engineered to express a CAR that specifically recognizes a tumor-associated antigen expressed on the cancer cell's surface. The CAR consists of an antibody fragment (single-chain variable fragment [scFv]) responsible for antigen recognition that is linked to a transmembrane domain and the CD3ζ intracellular signaling domain of T cells, either alone or more commonly in combination with T cell co-stimulatory domains, such as CD28 (Figure 1).