BACKGROUND
Metastatic colorectal cancer (mCRC) is one of the major causes of death worldwide. The relative therapeutic resistance of these populations to I/O drives the need for new treatment. STC-1010 (Brenus Pharma) therapeutic vaccine is developed by tumor cells stimulation to induce overexpression of TAA and neoantigens to mimic mCRC resistant cancer cells allowing education of the immune system to target the patient’s tumor cells harboring the same resistance factors. We report results of a study evaluating efficacy and safety of a 3 cell lines-based product namely “3CL-SH” (made of CT26, CMT93 and LTPA) physical stimulated (S=irradiation and heat shock) and haptenized (H) with immunostimulant in an anti-PD1 resistant MC38 colorectal tumor model grafted with its TME.
METHODS
Female C57BL/6 mice bearing MC38 tumor model grown in vivo under anti-PD1 selection pressure (anti-PD1; 12.5 mg/kg; qw) to obtain MC38 resistant to anti-PD1 treatment (MC38 antiPD1R). Two sampled tumors from these mice were cut into fragment of 2 mm2 and reimplanted in the right flank of naïve syngenic mice. 5 groups (15 mice per group) were allocated to: G1) Control group: Isotype/placebo/vehicle G2) Anti-PD1/placebo/vehicule G3) Anti PD1/placebo-GM-CSF/endoxan G4) Isotype/3CL-SH-GM-CSF/endoxan G5) Anti-PD1/3CL-SH-GM-CSF/endoxan. Endoxan, vehicule and antibodies were administered by IP, vaccine or placebo subcutaneously. Overall survival (OS) and tumour growth (TG) were recorded until 1600 mm3 or safety endpoint. 5 mice per group were euthanized and sampled for immunophenotyping. In parallel, we conducted the identification and relative quantification of proteins expressed in 3CL-SH by LC-MS/MS and flow cytometry.
RESULTS
