title: Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma.
abstract: Allogeneic hematopoietic SCT (HSCT) has been shown to be an effective treatment option for advanced renal cell cancer (RCC). However, tumor resistance/relapse remains as the main post transplant issue. Therefore, enhancing graft-versus-tumor (GVT) activity without increasing GVHD is critical for improving the outcome of HSCT. We explored the GVT effect of haploidentical-SCT (haplo-SCT) against RCC in murine models. Lethally irradiated CB6F1 (H2K(b/d)) recipients were transplanted with T-cell-depleted BM cells from B6CBAF1 (H2K(b/k)) mice. Haplo-SCT combined with a low-dose haploidentical (HI) T-cell infusion (1 × 10(5)) successfully provided GVT activity without incurring GVHD. This effect elicited murine RCC growth control and consequently displayed a comparative survival advantage of haplo-SCT recipients when compared with MHC-matched (B6D2F1CB6F1) and parent-F1 (B6CB6F1) transplant recipients. Recipients of haplo-SCT had an increase in donor-derived splenic T-cell numbers, T-cell proliferation and IFN-γ-secreting donor-derived T-cells, a critical aspect for anti-tumor activity. The splenocytes from B6CBAF1 mice had a higher cytotoxicity against RENCA cells than the splenocytes from B6 and B6D2F1 donors after tumor challenge. These findings suggest that haplo-SCT might be an innovative immunotherapeutic platform for solid tumors, particularly for renal cell carcinoma.
authors: Department of Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Onder.Alpdogan@jefferson.edu
authors: T
authors: T
authors: Budak-Alpdogan
authors: C T
authors: CT
authors: Sauter
authors: C P
authors: CP
authors: Bailey
authors: C S
authors: CS
authors: Biswas
authors: M M
authors: MM
authors: Panis
authors: S
authors: S
authors: Civriz
authors: N
authors: N
authors: Flomenberg
authors: O
authors: O
authors: Alpdogan
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000601:surgery*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA