The applicant has strong preliminary data in several rodent cancer model systems and in patients with intraductal cell carcinoma of the breast (BC) illustrating that all tumor types tested consistently express an autoimmunogenic, shared 44kD oncofetal antigen (OFA) as well as an unshared tumor specific transplantation-like antigen (TSTA). The usefulness of 44kD OFA or its peptide components as a vaccine to activate T-cell mediated immunity adequate to prevent primary tumor induction in rodents subjected to two """"""""carcinogens"""""""" will be investigated. OFA is closely related or identical to an immature form of Laminin Receptor Protein (iLRP approximately equal to OFA) by peptide and DNA sequence analysis. The applicant's three aims are: 1). To test the capacity of both the mouse embryo encoded r iLRP expressed in E. coli and the purified mouse 44kD OFA extracted from x-ray induced lymphomas or sarcomas to stimulate T-cell immunity in inbred rodents when used as a """"""""vaccine"""""""" so as to interrupt the primary carcinogenesis process caused by 3-methylcholanthrene (3-MCA) skin exposure in BALB/c mice or produced by fractioned doses of sub-lethal X-irradiation (fX) in RFM and B-10 mice; 2). To test the capacity of ex vivo derived OFA- or TSTA-specific CD4 TdTH lymphocyte clones and CD8 T cytotoxic (Tc) clones, restimulated and expanded in vitro with either OFA or iLRP, to passively protect naive, normal mice against OFA+ 3-MCA induced sarcoma cell or X-ray-induced leukemia cell challenge using adoptive transfer methods. Likewise, he seeks to test CD8, non-cytotoxic OFA-specific T-suppressor (Ts) lymphocytes which secrete IL-10 lymphokine to determine if they can enhance tumor development following direct challenge with tumor cells or in mice developing primary X-ray or 3-MCA induced primary tumors when used to interrupt oncogenesis; 3). To determine if peptides present in OFA or iLRP can be used to expand protective cytotoxic (Tc) clones or tumor promoting Ts clones which are capable of interrupting primary tumor development when used as a vaccine or when these activated T-cell clones are adoptively transferred.
| Rohrer, James W; Barsoum, Adel L; Coggin Jr, Joseph H (2006) Identification of oncofetal antigen/immature laminin receptor protein epitopes that activate BALB/c mouse OFA/iLRP-specific effector and regulatory T cell clones. J Immunol 176:2844-56 |
| Coggin Jr, Joseph H; Barsoum, Adel L; Rohrer, James W et al. (2005) Contemporary definitions of tumor specific antigens, immunogens and markers as related to the adaptive responses of the cancer-bearing host. Anticancer Res 25:2345-55 |
| Siegel, Sandra; Wagner, Andreas; Kabelitz, Dieter et al. (2003) Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies. Blood 102:4416-23 |
