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| Tumor Immunology and Immunotherapy | |||||||
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The research in the laboratory focuses on tumor immunology and immunotherapy with an emphasis on the development of therapeutic vaccines for prostate cancer. Toward that end we have developed a vaccine in which the gene for prostate specific antigen (PSA) has been inserted into a replication deficient adenovirus. This adenovirus/PSA (Ad/PSA) vaccine has been shown to induce strong anti-PSA immune responses as evidenced by the presence of anti-PSA antibodies and anti-PSA T cells. Protective immunity to a challenge with PSA-secreting mouse prostate tumor cells can be demonstrated in mice immunized with the vaccine. The destruction of established tumors can be accomplished by the combination of Ad/PSA vaccine immunization and cytokine gene therapy using viruses that produce IL2, IL12, and TNFα. We are also investigating the augmentation and modulation of anti-tumor immune responses by the use of CpG oligodeoxynucleotides and the development of other microbial vaccines that would induce vigorous anti-prostate tumor immunity.
We have recently completed a Phase I clinicla trail of the Ad/PSA vaccine in men with prostate cancer. The main purpose of a Phase I trail is to provie evidence of the safety of the product, in this case a tumor vaccine. None of the 32 patients immunized with the vaccine showed any serious vaccine-related side effects proving its safety. We have begun a therapeutic Phase II trial in patients with recurrent prostate cancer. Collaborations with the laboratory of Dr. Susan Lutgendorf are addressing the role of psychological factors on immune function in women with ovarian, cervical, and breast cancers and the role these factors may have on disease progression. |
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| Selected Publications | |||||||
| Click Here for a Complete List of Articles | |||||||
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Lubaroff D.M., Karan, D., Andrews, M.P., Acosta, A., Abouassaly, C., Sharma, M. and Krieg, A.M. Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer. Vaccine, 24:6155-6162, 2006.
Lubaroff D.M., Konety, B., Link, B.K., Ratliff, T.L. and Williams, R.D. A Phase I study of an adenovirus/PSA vaccine in men with metastatic prostate cancer. Human Gene Therapy, 17:220-229, 2006. Karan, D. and Lubaroff D.M. Paradoxical enhancement of CD8 T cell-dependent anti-tumor protection despite suppressed CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine. Int. J Cancer, 121:1520-1528, 2007. Hendrix, M.J.C., Luo, J., Seftor, E.A., Sharma, N., Heidger, P.M. Jr., Cohen, M.B., Bhatty, R., Chunthapong, J., Seftor, R.E.B. and Lubaroff D.M. Epithelial-mesenchymal molecular interactions in prostatic tumor cell plasticity. In: Metastasis Cancer of Prostate, edited by R.L. Ablin and M.D. Mason. The Netherlands: Springer Academic Publishers, 10:127-141, 2007. Lamkin, D.M., Lutgendorf, S.K., McGinn, S., Dao, M., Maiseri, H., DeGeest, K., Sood, A.K. and Lubaroff D.M. Positive psychosocial factors and NKT cells in ovarian cancer patients. Brain Behavior Immunity, 22:65-73, 2008. |
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| Department/Program Affiliations |
| Urology |
| Biosciences |
| Immunology |
| Microbiology |