Oncolytic Virus Therapy for Cancer
Oncolytic viruses are emerging therapeutic agents for cancer. They have the capacity to infect tumor cells, replicate therein, lyse the cells and release progeny virus, which infect neighboring cells. The lytic cell death induced by the virus is not dependent on the ability of the tumor cell to go into apoptosis, thus also drug-resistant cancer stem cells can be killed. Furthermore, the presence of immunogenic virus in the tumor microenvironment can alter the otherwise immunosuppressive milieu in favor of an anti-tumor immune response.
We are developing genetically engineered viruses for cancer therapy. We focus our efforts on prostate cancer and neuroendocrine tumors. Virus replication is controlled by tissue-specific promoters and further restricted by introduction of tissue-specific microRNA target sequences in the viral genome. The infectivity is also altered through genetic modification of virus capsid to favor infection of tumors cells. In order to target metastatic sites we are evaluating various cell types as vehicles to deliver virus at the tumor site. We are in particular looking at tumor antigen-restricted T cells, which target tumor cells directly, and macrophages and mesenchymal stem cells, which are attracted to the inflammatory environment of the tumor.
T Cell Therapy for Cancer and Virus Infections
Adoptive transfer of antigen-specific T cells in combination with host immune-depletion has during the last years emerged as an interesting therapeutic approach to combat severe virus infection and cancer.
We have long experience in isolating and expanding antigen-specific T cells from peripheral blood and we have developed a rapid protocol for simultaneous activation and expansion of cytomegalovirus (CMV)-directed cytolytic and helper T cells. The protocol has great potential to treat transplant patients who suffers from CMV disease due to their immunosuppressive medication. We also have long experience with T cells directed against tumor-associated antigens and we have shown that prostate cancer patients have an increased frequency of prostate antigen-specific T cells in their blood. We are developing genetically engineered T cells, expressing T cell receptors or chimeric antigen receptors with specificity for prostate tumor-associated antigens. The T cells are further modified to be resistant to suppressive factors in the tumor microenvironment. That way large numbers of antigen-specific cytolytic T cells can be rapidly obtained for adoptive transfer to cancer patients.