Vaccinia virus‐infected C‐C36 colon tumor cell lysates stimulate cellular responses in vitro and protect syngeneic balb/c mice from tumor cell challenge

Abstract

Vaccinia virus (VV) was used to infect and lyse the Balb/c colon tumor line C-C36 to prepare oncolysate (VCO) with augmented immunogenicity. Mice treated with VCO and challenged with C-C36 were significantly protected against tumor growth as compared to untreated controls (P less than 0.001) and mice treated with CO (P less than 0.01). Moreover, protection induced by VCO was specific when growth inhibition of C-C36 was compared to that of meth-A (P = 0.027). Splenocytes from mice stimulated with VCO in vitro showed greater proliferation than splenocytes stimulated with CO alone or VV alone, suggesting induction of a unique VCO component. Additional evidence for a specific response was suggested by the observation that splenocytes stimulated with VCO in vitro demonstrated augmented cytolysis of C-C36 but did not show cytolytic activity against unrelated target cells. However, augmented cytolysis of the natural killer (NK)-sensitive YAC-1 by VCO-stimulated splenocytes was also observed. These results suggest that in vivo resistance to tumor challenge induced by VCO treatment may result from stimulation of both specific and nonspecific effector cells.

Carbon Nanotubes Conjugated to Tumor Lysate Protein Enhance the Efficacy of an Antitumor Immunotherapy

“…Because the nature of the immunogens was not known, the efficacy of therapy involving the tumor lysate proteins was generally assessed by tumor rejection, tumor growth retardation, or prolonged survival of the immunized mice but not by antibody production 40. Nevertheless, human clinical studies based on such vaccines have shown promising results in some of the trials 29, 41–46. Fifis et al48 have reported that carboxylated polystyrene nanospheres conjugated to ovalbumin (OVA) can significantly enhance the immune reaction against an OVA‐expressing tumor.…”

“…Tumor lysate protein contains a mixture of various tumor proteins. Unlike tumor‐specific antigens that are rare and difficult to obtain,40 tumor lysate proteins are readily obtainable and have been investigated in antitumor immunotherapy studies with promising results 21, 41–45…”

A Novel Dendritic Cell-Based Cancer Vaccine Produces Promising Results in a Syngenic CC-36 Murine Colon Adenocarcinoma Model

“…Prior to its use as a human melanoma vaccine, the first generation VMO vaccine was tested in mice with CC-36 colon adenocarcinoma [13]. In the present study, the same murine model was used to evaluate the efficacy of our second generation cancer vaccine composed of DCs pulsed with a recombinant IL-2-vaccinia virusaugmented colon tumor cell lysate (DC-IL-2VCO).…”

Active specific immunotherapy with vaccinia colon oncolysate enhances the immunomodulatory and antitumor effects of interleukin-2 and interferon α in a murine hepatic metastasis model

“…Heterogenization of tumor by viruses is one such approach [12,43,44]. In our laboratory, we have used vaccinia-virus-infected cell lysates in murine models in which preimmunization induced resistance to challenge [21,50,51], and have previously shown that combined active specific immunotherapy with vaccinia colon oncolysate (VCO) and low-dose IL-2 demonstrated synergy in the reduction of tumor burden and increase in survival in a murine CC-36 colon tumor hepatic metastases model [2,3].…”