Treatments with cytotoxic agents or viruses may result in Immunogenic Cell Death (ICD), which immunizes tumor-bearing hosts but does not result in complete tumor regression. The researchers hypothesize that combining two ICD inducers will result in long-term regression in immunocompetent mice. In vitro, ICD was optimized by increasing calreticulin externalization in human colorectal carcinoma (CRC) cells by exposing them to Oxaliplatin (OX) and human adenovirus mixtures (AdV). Six-millimeter-diameter CT26 or 4T1 carcinomas in the flanks of BALB/c mice were injected once intratumorally (IT) with OX, AdV, or a combination of the two. Tumor growth, tumor-infiltrating lymphocytes (TIL), nodal cytotoxicity, and rejection of a viable cell challenge were all measured. Tumors were injected with an optimal mixture of 80 M once. The volume of OX – AdV 25 Multiplicity of Infection (MOI) tumors in the PBS buffer was 17–29 percent that of control tumors. When the buffer was changed from PBS to 5% dextrose in water (D5W), the volume of tumors injected IT with 80 M decreased. OX-AdV 25 MOI were 10%, while IT OX or AdV alone were 32% and 40% of the volume of IT buffer-treated tumors, respectively. OX-AdV IT increased CD3+ TIL by fourfold, decreased CD8+ PD-1+ TIL from 79% to 19%, and induced cytotoxicity to CT26 cells in draining node lymphocytes, whereas lymphocytes from untreated CT26-bearing mice were not cytotoxic. OX-AdV IT caused complete regression in 40% of D5W mice.
CT26 contralateral challenge was rejected by long-term survivors. The buffer for Oxaliplatin is critical. The combination of the two ICD inducers shows promise as an agnostic sensitizer for carcinomas such as colorectal carcinoma.