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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 48; no. 8; pp. 1084 - 1090
• Main Authors: Budak-Alpdogan, T, Sauter, C T, Bailey, C P, Biswas, C S, Panis, M M, Civriz, S, Flomenberg, N, Alpdogan, O
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2013; Nature Publishing Group
• Subjects: 631/250/1904; 692/699/249/1529; 692/699/67/589/1588/1351; Allografts; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animal models; Animals; Anticancer properties; Antitumor agents; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer; Carcinoma, Renal cell; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - surgery; Care and treatment; Cell Biology; Cell Line, Tumor; Cell proliferation; Cytotoxicity; Disease Models, Animal; Female; Graft versus host reaction; Graft vs Tumor Effect - immunology; Haploidy; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Internal Medicine; Kidney cancer; Kidney Neoplasms - immunology; Kidney Neoplasms - surgery; Kidneys; Lymphocytes T; Major histocompatibility complex; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Nephrology. Urinary tract diseases; original-article; Public Health; Renal cell carcinoma; Solid tumors; Spleen; Splenocytes; Stem cell transplantation; Stem Cells; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Tumors; Tumors of the urinary system; γ-Interferon; United States; animal models; GVHD; renal cell cancer; haploidentical hematopoietic SCT; graft-versus-tumor effect; Kidney disease; Immunopathology; Graft versus host disease; Animal model; Haploidentical graft; Urinary system disease; Carcinoma; Hematology; Graft versus tumor reaction; Stem cell; Hematopoietic cell; Malignant tumor; Kidney cancer; Grawitz tumor; Hematopoietic stem cell transplantation; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2013.9

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.