Edmund C. Lattime, PhD Division of Surgical Oncology

The primary focus of our laboratory is the study of the tumor host interaction with the ultimate goal being the design of effective immunotherapy regimens for cancer. The interaction between the host immune system and tumor is a multifaceted one with the generation of productive immunity requiring the cooperation of immune cells from multiple lineages. Tumor recognition involves the expression of a number of cell surface molecules and once activated, lymphocytes produce a cascade of regulatory factors leading to the expression of localized and systemic immune responses. Further complicating the system, tumor cells themselves can produce immune suppressive factors.

In studies of human melanoma and bladder cancer with relevant murine models of each, our laboratory has characterized the tumor host interaction and is the first to have shown that the cytokine IL10 which down regulates the development of cellular immunity is produced in both types of cancer in-vivo. In addition, we have discovered that epithelial bladder tumor cells are capable of presenting soluble antigens to the immune system, thus suggesting a new approach to tumor immunotherapy.

Following the above characterization, a significant focus of current studies in our laboratory lies in the development of genetic approaches towards immunotherapy. Recombinant vaccinia virus vectors are being explored as a means of transfecting tumor cells in-vivo in-situ with the ultimate goal of enhancing immunity. In this approach, viruses are engineered to contain the genes for immunologic helper factors such that when injected into tumors, they infect the tumor cells and cause the infected tumor to produce the enhancing cytokines. In a related approach, viruses are also being engineered to inhibit the production of tumor produced factors such as IL10 above which suppress the immune response.

Most recently, studies in our laboratory have included a new initiative towards the design of genetic vaccine strategies for breast cancer. Given an enhanced understanding of how immune responses are not only initiated but focused towards cell mediated or humoral (antibody producing) arms, we are in the process of “designing” genetic vaccines which will enhance the specific arms of an immune response. This latter focus will be greatly enhanced by the outstanding clinical and basic science resources focused on breast cancer at The Cancer Institute of New Jersey.

Recent Publications

• Halak B.K., Maguire H.C. Jr., Lattime E.C. Tumor-associated IL10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site Cancer Research 1999, 59:911-917.
• Mastrangelo M.J., Maguire H.C. Jr., Eisenlohr L.C., Laughlin C.E., Monken C.E., McCue P.A., Kovatich A.J., Lattime E.C. Intratumoral recombinant GM-CSF encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Therapy 1999, 6:409-422.
• Gomella L.G., Mastrangelo M.J., McCue P.A., Maguire H.C. Jr., Mulholland, S.G., Lattime E.C. Phase I study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer. J. Urology 166(4):1291-5. 2001.
• Mastrangelo M.J. and Lattime E.C. Virotherapy clinical trials for regional disease: In-situ immune modulation using recombinant poxvirus vectors. Cancer Gene Therapy 9:1013-1021, 2002.
• Yang A.S., Lattime E.C. Tumor-induced IL-10 Suppresses the Ability of Splenic Dendritic Cells to Stimulate CD4 and CD8 T Cell Responses. Cancer Res. 63:2150-2157. 2003.
• Yang A.S., Monken C.E., Lattime E.C. Intratumoral vaccination with vaccinia expressed tumor antigen and GM-CSF overcomes immunological ignorance to tumor antigen. Cancer Research (in press). 2003.
• Strair R.K., Schaar D., Medina D., Todd M.B., Aisner J., DiPaola R.S., Manago J., Knox B., Jenkinson A., Senzon R., Baker C., Dudek L., Ciardella M., Kuriyan M., Rubin A. and Lattime E.C. Anti-neoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma. J. Clin., Oncol. (in press). 2003.