1. Jinan Baofa Cancer hospital, Jinan, Shandong Province, China, 250000.
2. Beijing Baofa Cancer Hospital, Beijing, China, 100010.
3. Immune Oncology Systems, Inc, San Diego, CA, USA, 92102.
4. Huanan Hospital, Shenzhen University, Shenzhen, Guangdong, China, 518055.
5. TaiMei Baofa Cancer hospital, Dongping, Shandong Province, China, 271500.
Intratumoral immunotherapy is well studied and is ongoing, but few studies have evaluated the relationship between of cytotoxic drugs intratumoral injection (CDI) and hapten-enhanced cytotoxic drugs intratumoral injection (HECDI) and patient survival. The objectives of this study include comparisons to explore possible associations between the proportions of treatment-induced cytokines and autologous antibodies to tumor-associated antigens (TAAs) and the relative size of the abscopal effects concurring. CDIs contain oxidant and cytotoxic drugs, HECDIs contains the same drug plus penicillin as the new Hapten. Of the 33 patients with advanced pancreatic cancer, 9 received CDI, 20 received HECDI, and 4 (control group) received placebo. Serum levels of cytokines and autoantibodies of TAAs were detected and compared after therapy. The 1-year survival rate was 11.11% for CDI and 52.63% for HECDI (P= 0.035). In the general analysis of cytokines, HECDI exhibited an increasing level of IFN-γ and IL-4, and the non-hapten CDI showed a rising level of IL-12 (P = 0.125, 0.607, & 0.04). Participants who did not receive chemotherapy had significant differences in the level of Zeta autoantibody only before and after HECDI; However, IMP1 levels in patients with previous chemotherapy experience were significantly different before and after HECDI and CDI treatment (P≤0.05, P = 0.316). After HECDI treatment, TAA autoantibodies of RalA, Zeta, HCC1, p16 increased (P = 0.429, 0.416, 0.042, 0.112). The elevated levels of CXCL8, IFN-γ, HCC1, RalA, Zeta, and p16 observed in HECDI may be attributed to the abscopal effect (P = 0.012 & 0.013). Overall survival rates indicated that HECDI treatment extended participants' lives.
Keywords: Penicillin, Intratumoral injection, Cancer immunotherapy, Drug delivery, Extracellular matrix as a drug carrier, Autologous coagulum, Intracellular drug delivery