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Determination of Patients' Breast Tumor-Specific Immunity and Its Enhancement with In Vitro Stimulation and Gene Therapy

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Final rept. 1 Oct 94-30 Sep 97

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During the three years of our Army support, we have successfully completed the majority of the Specific Aims. We have succeeded in developing a model system for the growth of patients primary breast tumors in the SCID mouse and this has appeared in print. We have correlated the growth pattern of these tumors in the SCID mouse model with clinical data concerning the diagnosis, treatment and prognosis of the patients. This suggests that ER negative status andor prior chemotherapy is related to fast growth in SCID mice and poor patient prognosis. Immunohistochemical labelling of tumors grown in SCID mice demonstrates that important tumor markers are expressed in this tumor model HER-2neu, CD40 and CD40L, Fas and FasL, CD34, and MHC class I. Tumors have been collected in sequential passages over the duration of our study months to years and phenotyping of these tumors is in progress. Preliminary results suggest that with the disease progression in SCID mice, the expression of new antigens may occur while other markers may be down regulated. The effect of whole body hyperthermia WBH on reduction of human breast tumor in our model has appeared in print. Our evidence shows that WBH enhances tumor immunogenicity by increasing expression ofheat shock proteins and host NK cell killing. Our efforts to identify tumor antigens using human antibodies present in the sera of tumor bearing SCID mice and by the generation of autologous T cell clones show the potential of this model for future development of cancer immunotherapies.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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