A novel idea and method for a new generation of cancer vaccine

Abstract

1876

Introduction:

The main obstacles for a successful cancer vaccine are the poor immunogenicity of tumors, the unavailability of suitable methods of preparing tumor cells for in vitro sensitization, and the inability to achieve a large number of activated early stage immune cells. It is also difficult to establish an animal model similar to clinical settings. There is a need to improve current cancer vaccine and to develop alternative strategies.

Materials and Methods:

Tumor cells from cell lines (liver, colon, ovary, lung, and breast cancer) obtained from ATCC were seeded and cultured in an innovative three dimensional (3D) tissue culture device to rebuild tumors in vitro. Mononuclear cells (MNCs) were co-cultured with the rebuilt tumor for in vitro sensitization in an environment mimicking in vivo cellular immunization. After separation from the tumor cell by gradient density and proliferation by a method similar to the expansion of tumor infiltrating lymphocytes, a group of activated antitumor immune cells with no residual tumor cells was harvested for use.

Results:

The tumors rebuilt in vitro in a 3D environment exhibited biologic and cellular characteristics similar to that of malignant tumors in vivo and expressed tumor antigens. When MNCs were co-cultured with these tumors, dynamic interactions among immune and tumor cells were observed:

Initial stage: Within 24 to 72 hours, the immune cells had efficient close contact with the tumor cells. The detailed process of the tumor antigen intake, processing and presentation by either dendritic cells or lymphocytes were observed.

Induced stage: After initiation, there was significant proliferation and differentiation of the immune cells. The differentiated lymphocytes were occasionally joined together as two or three cells unit to perform immune responses, such as antigen presentation.

Effective stage: Sensitized immune cells actively searched for and attached to tumor cells and limited their growth. These immune cells were also actively involved in the immune surveillance to prevent the metastasis of the tumor. More importantly, these cells directly killed tumor cells through cytolysis by cytotoxic T lymphocytes or phagocytosis by activated macrophages.
>Conclusions:
>Our model may serve as a valuable tool to evaluate the cell-mediated immune response in vitro, such as determining the fate of transferred immune cells or the optimal strategies for enhancing their antitumor activity. Cytolysis and tumor regression can be used as more dependable measures of efficacy. This method improves the tumor antigen recognition, promotes the proliferation and differentiation of the immune cells, and demonstrates a broad range of potent antitumor effects. Large number of early stage effector T cells can be obtained, and these cells can kill target tumor cells ex vivo. This novel idea and innovative method could be used to create a new generation of powerful cancer vaccines for immunotherapy and immunoprophylaxis.