In vitro and in vivo Evidence on Intra-tumor Injection of Allogeneic Serum for Immunotherapy in a Mouse Model of Colon Cancer

Erfan Basirat; Danial Dehghan; Ardeshir Abbasi; Nafiseh Pakravan

doi:10.18502/ijaai.v21i5.11042

Erfan Basirat Student Research Committee, Medical School, Alborz University of Medical Sciences, Karaj, Iran
Danial Dehghan Student Research Committee, Medical School, Alborz University of Medical Sciences, Karaj, Iran
Ardeshir Abbasi Department of Immunology, Medical School, Tarbiat Modarres University, Tehran, Iran
Nafiseh Pakravan Division of Immunology, Medical School, Alborz University of Medical Sciences, Karaj, Iran

DOI: https://doi.org/10.18502/ijaai.v21i5.11042

Keywords: Allogeneic serum; Angiogenesis; Cluster of designation 38; Hypoxia-inducible factor 1; Alpha subunit; Interleukin-10; Matrix metalloproteinases

Abstract

It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor.

Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line. The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukin (IL)-10.

An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group.. In contrast, to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels.

A new approach to serum or plasma therapy and allogeneic vaccines for cancer is the intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.