Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma

Creative Commons License

Budak-Alpdogan T., Sauter C. T., Bailey C. P., Biswas C. S., Panis M. M., Civriz S., ...Daha Fazla

BONE MARROW TRANSPLANTATION, cilt.48, sa.8, ss.1084-1090, 2013 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 48 Sayı: 8
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1038/bmt.2013.9
  • Dergi Adı: BONE MARROW TRANSPLANTATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1084-1090
  • Anahtar Kelimeler: renal cell cancer, animal models, graft-versus-tumor effect, GVHD, haploidentical hematopoietic SCT, BONE-MARROW-TRANSPLANTATION, NATURAL-KILLER-CELLS, SOLID TUMORS, HOST-DISEASE, NK CELLS, T-CELLS, CANCER, LIGAND, CYCLOPHOSPHAMIDE, INFUSION
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Ankara Üniversitesi Adresli: Hayır

Özet

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 x 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-gamma-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.