Tumor protein D52 (D52) is constitutively expressed in healthy tissues and overexpressed in multiple cancers, including (but not limited to) breast, prostate and ovarian carcinomas. Although the normal functions of D52 are unknown, it is clear that increased D52 expression levels not only stimulate cell proliferation and metastasis, but also correlate with poor prognosis in a subset of breast cancer patients. The murine orthologs of D52 (mD52) shares 86% identity with its human counterpart (hD52) and mirrors hD52 expression patterns. The forced overexpression of mD52 induces anchorage-independent growth in vitro and promotes tumor formation as well as spontaneous metastasis in vivo. We have previously reported that the intramuscular administration of recombinant mD52 elicits immune responses capable of rejecting a challenge with tumor cells and preventing spontaneous metastasis only in 50% of mice. We hypothesized that mechanisms of peripheral tolerance dampen immune responses against mD52, thus limiting the protective effects of vaccination. To test this hypothesis, mice were depleted of CD25+ regulatory T cells (Tregs) and subcutaneously immunized with mD52 prior to a tumor challenge. The subcutaneous immunization failed to induce protective antitumor immunity unless accompanied by Treg depletion, which resulted in a rate of protection of 70% as compared with

It is a clinically and experimentally well supported working hypothesis that infection with hepatitis B virus may result in chronic active hepatitis in patients with suspected immune deficiencies. On this basis, a pilot study was performed in order to evaluate the effect of "specific" transfer factor (TF) in the treatment of HBS-Ag-positive chronic active hepatitis. From the leukocytes of 500 ml venous blood each of 40 volunteers that had completely recovered from acute virus hepatitis B within the last 6 months, a unique TF pool (40 units of TF) was prepared according to the method of Lawrence. Preexaminations indicated that this preparation was able to enhance cellular immune reactions in vitro. Thirteen patients with HBS-antigenemia and chronic active hepatitis (i.e., two liver biopsies within the last 6 or more months with the histological criteria of chronic aggressive hepatitis according to de Groote, elevated serum levels of bilirubin, alkaline phosphatase, transaminase activities, and/or gamma-globulines) were randomized: Seven received s.c. injections of two units of TF each on days 1 and 15, the other six saline. Conversion of skin reactions to some ubiquitous antigens occurred in the TF group, but no significant and constant drop of HBS-Ag serum titers was observed. Although some of the biochemical parameters seemed to ameliorate in the TF group, the differences versus the control group did not prove to be significant within the limited number of patients under observation. The in vitro reactivity of patients' lymphocytes to HBS-Ag, tested by means of the 3H-thymidine uptake, was never found enhanced after TF application. In the used doses, "specific" TF was not effective in the treatment of HBS-Ag-positive chronic active hepatitis; unfavorable side-effects were not observed.

Tumor protein D52 (TPD52) is a novel auto-antigen involved in cellular transformation, proliferation and metastasis. Its over-expression has been demonstrated in several human malignancies including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and spontaneous metastasis in vivo. Importantly, mD52 mirrors the function and normal tissue expression patterns of the human orthologue of TPD52 (hD52) and shares 86% identity at the amino acid level. Thus, TPD52 represents a self, non-mutated tumor associated auto-antigen that is important for maintaining a tumorigenic phenotype. The Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) model was employed to study TPD52 as a vaccine antigen. Naïve mice were immunized with either mD52 or hD52 DNA. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Greater than 70% of mice were tumor free more than 10 months post tumor challenge when immunized with hD52 as a xenogenic DNA vaccine. Survivors of the initial tumor challenge rejected a second tumor challenge with TRAMP-C2 tumor cells given in the opposite flank approximately 138 days after the first challenge with TRAMP-C1, and remained tumor free for more than 6 months. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a cellular immune response was involved in tumor rejection. These data suggest that hD52 xenogeneic DNA vaccination induced a memory, cellular immune response that resulted in superior protection from challenge with murine prostate-derived tumors that naturally over-express mD52 protein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4791.