GENETICALLY REGULATED RESPONSE TO INTRAVESICAL BACILLUS-CALMETTE-GUERIN IMMUNOTHERAPY OF ORTHOTOPIC MURINE BLADDER-TUMOR

Purpose: Genetically regulated host response to intravesical Bacillus Calmette Guerin (BCG) immunotherapy was assessed using the murine blad der tumor MM45T in Bcg(r) and Bcg(s) inbred congenic strains of mice. Materials and Methods: Tumor detection and monitoring of treatment res ponse to BCG was carried out using magnetic resonance imaging (MRI) of BALB/c (Bcg(s) allele) and BALB/c.CD2 (CD2) (Bcg(r) allele) mice impl anted orthotopically with MM45T tumor cells. Intravesical BCG instilla tion (3 doses per week for 3 weeks) was used as prophylaxis against tu mor implantation in both Bcg(r) and Bcg(s) strains and as definitive t reatment against MRI-confirmed established tumors. Tumors implanted in both strains of untreated mice served as controls. Intravesical injec tion of BCG was also performed in established heterotopic subcutaneous tumors in both strains. Immunologic response in all groups was assess ed by flow cytometric analysis of the bladder irrigation fluid cell co mposition, measuring CD4(+) (helper/inducer) and CD8(+) (cytotoxic/sup pressor) cell subsets. Results: Intralesional injection of BCG into es tablished heterotopic tumors showed growth inhibition in the Bcg(s) st rain but not in the Bcg(r) strain. Intravesical BCG treatment against established orthotopic tumors showed significant tumor regression in t he Bcg(s) strain compared to control but there was no effect in the Bc g(r) strain. Conclusion: The differential anti-tumor activity of BCG i n the Bcg(s) and Bcg(r) congenic murine strains supports the notion th at Beg gene-controlled responsiveness to BCG innoculation determines, at least partially, the host response to immunotherapy. These results have potential clinical significance in patient selection for intraves ical therapy for bladder cancer.