Journal of Immunology. 2006 Mar 1;176(5):2844-56.

Identification of oncofetal antigen/immature laminin receptor protein epitopes that activate BALB/c mouse OFA/iLRP-specific effector and regulatory T cell clones.

Rohrer JW, Barsoum AL, Coggin JH Jr.

Department of Microbiology and Immunology, University of South Alabama College of Medicine, Mobile, AL 36688-0002, USA. jrohrer@jaguar1.usouthal.edu

During tumor development in mice and humans, oncofetal Ag/immature laminin receptor (OFA/iLRP)-specific Th1, CTL, and IL-10-secreting T (Ts) cells are induced. The presence of too many Ts or too few effector T cells appears to predict a poor prognosis. We established clones of OFA/iLRP-specific splenic Th1, CTL, and Ts cells from the OFA/iLRP+ MCA1315 fibrosarcoma-bearing BALB/c mice or from BALB/c mice vaccinated with 1 or 10 microg of rOFA/iLRP. The MCA1315 tumor cell-reactive T cell clones were characterized as to surface Ag phenotype, cytokine secretion profile, and specificity for OFA/iLRP presented by syngeneic splenic APC. OFA/iLRP-specific Th1 and Ts clones were established from all mice. OFA/iLRP-specific CTL could be established from all mice except for mice immunized with 10 microg of rOFA/iLRP. Analysis of the proliferation profile of the OFA/iLRP-specific clones to overlapping OFA/iLRP 12-mer peptides that spanned the OFA/iLRP protein sequence defined the epitopes to which the T cell clones responded. There was a similar spatial distribution of the epitopes to which the two types of CD8 T cell clones responded. The nonapeptide epitopes of the Ts clones were located between aa 36 and 147 of OFA/iLRP, while the epitopes of the CTL clones were located between aa 52 and 163. Even though the CTL and Ts epitopes shared part of the protein, all of the CD8 CTL epitopes were distinct and separable from those of CD8 Ts cells.

PMID: 16493041 [PubMed - indexed for MEDLINE]

Anticancer Research. 2005 May-Jun;25(3c):2345-55.

Contemporary definitions of tumor specific antigens, immunogens and markers as related to the adaptive responses of the cancer-bearing host.

Coggin JH Jr, Barsoum AL, Rohrer JW, Thurnher M, Zeis M.

University of South Alabama, College of Medicine, Department of Microbiology and Immunology, Mobile, AL 36688, USA. jcoggin@jaguarl.usouthal.edu

This review describes clear parameters for designating the correct use of the term Tumor Rejection Antigen [TRA] to define the role of tumor cell constituents which activate adaptive anti-tumor immune reactions in the cancer-bearing host. This is important, especially in defining immunogens which activate the patient's cytotoxic T-cells that are important to immunotherapeutic applications in human cancer treatment. The focus of the review is to correctly delineate the immunogenic properties of 37 kDa oncofetal antigen [OFA], one of only a few true TRAs expressed on human and experimental rodent cancers. The purpose of this review is to provide a background for publication reviewers, journal and text editors, and scientists reporting on TRAs to avoid creating further confusion that has proliferated in the cancer literature to imply traits of so-called tumor-associated antigens that do not qualify as TRAs.

PMID: 16080461 [PubMed - indexed for MEDLINE]

Clinical Cancer Research. 2002 Nov;8(11):3369-76.

Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells.

Höltl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH Jr, Thurnher M.

Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria.

PURPOSE: We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2. RESULTS: Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive. CONCLUSIONS: Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.

PMID: 12429623 [PubMed - indexed for MEDLINE]

Journal of Urology. 2001 May;165(5):1705-9.

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

Zelle-Rieser C, Barsoum AL, Sallusto F, Ramoner R, Rohrer JW, Höltl L, Bartsch G, Coggin JH JR, Thurnher M.

Department of Urology, University of Innsbruck, Innsbruck, Austria.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

PMID: 11342960 [PubMed - indexed for MEDLINE]