The hypothesis to be tested in this pilot research project is that chemokines can improve the immunotherapy of cancer. The specific goals of this proposal are to test the ability of several selected chemokines to reduce tumor growth in both murine immunotherapeutic and immunoprophylactic models. Immunotherapy of cancer covers a very broad field of modalities that show both theoretical and experimental promise for effective treatment. Cancer vaccines offer superior theoretical therapy because they can induce long-term immunity directed specifically against tumor cells. Clinical trials with cancer vaccines show promise but reveal that immune responses are often weak or not wide spread (antigen immunogenicity problems), or that immune responses are against irrelevant antigens (antigen heterogeneity problems). Increasing the number of responding patients and increasing their immune responses to relevant tumor antigens is a prime goal of cancer vaccine therapy and the ultimate goal of this research. Chemokines appear to be ideal agents to accomplish these tasks. Chemokines attract, activate, and increase growth of specific target cells, especially antigen presenting cells (APC's). APC's are vital cells responsible for initiation of all immune responses. Chemokines that target APC's offer the best opportunity to initiate immune responses to tumor antigens found in existing tumors or cancer vaccines. We will examine the ability of these chemokines to reduce tumor growth by direct injection into existing murine tumors in the immunotherapeutic model. In this system the tumors essentially act as their own vaccines and eliminate antigen heterogeneity problems. When specific tumor antigens are known to be expressed on tumors, cancer vaccines containing these antigens may be used but still may have weak immunogenicity problems. Chemokines may be effective in these cases essentially acting as adjuvants, boosting immune responses by improving vaccine antigen presentation. We will examine this potential in an immunoprophylactic model. Mice will be immunized to antigens combined with chemokines then later challenged to lethal tumor doses. Chemokines that prove effective in these models could be directly translated to clinical trials under the direction of Dr. Jean-Claude Bystryn, the CoPI, at NYU Medical Center.
| Othoro, Caroline; Johnston, Dean; Lee, Rebecca et al. (2009) Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun 77:739-48 |
| Johnston, Dean; Zaidi, Bushra; Bystryn, Jean-Claude (2007) TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines. Cancer Immunol Immunother 56:1133-41 |
| Johnston, Dean; Reynolds, Sandra R; Bystryn, Jean-Claude (2006) Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice. Cancer Immunol Immunother 55:412-9 |
| Johnston, Dean; Bystryn, Jean-Claude (2006) Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine. Vaccine 24:1958-65 |
| Johnston, Dean; Bystryn, Jean-Claude (2005) Heterogeneous antibody response to polyvalent melanoma vaccines in syngeneic mice. Cancer Immunol Immunother 54:345-50 |
