Vaccination using well-characterized allogeneic tumor cell lines expressing standardized doses of immunostimulatory cytokines is an attractive alternative for autologous gene-transfected tumor cell vaccines. In the present study, we show that vaccination with irradiated allogeneic K1 735 (H-2k) or B16F10 (H-2b) melanoma cells induces a moderate degree of cross-protection against the M-3 melanoma (H-2d) in DBA/2 mice. Cross-protection against the syngeneic tumor was markedly improved when the allogeneic vaccines were transfected with the interleukin-2 (IL-2) gene. The IL-2 gene-modified allogeneic vaccines were effective for prophylactic vaccination against subsequent tumor challenge and for therapeutic vaccination against pre-existing tumor deposits, with efficacies that were comparable with that of the IL-2 gene-modified syngeneic vaccines. Cross-protection correlated with the cytotoxic activity of splenocytes against M-3 targets. Allogeneic vaccination was not effective in another model, against the B16F10 melanoma in C57BL/6 mice, irrespective of genetic modification with the IL-2 or granulocyte-macrophage colony-stimulating factor genes.
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http://dx.doi.org/10.1038/sj.cgt.7700183 | DOI Listing |
Haematologica
September 2024
Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California; Center for Definitive and Curative Medicine, Stanford University School of Medicine, Stanford.
Anti-CD117 monoclonal antibody (mAb) agents have emerged as exciting alternative conditioning strategies to traditional genotoxic irradiation or chemotherapy for both allogeneic and autologous gene-modified hematopoietic stem cell transplantation. Furthermore, these agents are concurrently being explored in the treatment of mast cell disorders. Despite promising results in animal models and more recently in patients, the short- and long-term effects of these treatments have not been fully explored.
View Article and Find Full Text PDFMol Ther
June 2024
UCL Great Ormond Street Institute of Child Health, Zayed Centre of Research, 20 Guilford Street, London WC1N 1DZ, UK; Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 1JH, UK. Electronic address:
Stem cell gene therapy and hematopoietic stem cell transplantation (SCT) require conditioning to ablate the recipient's hematopoietic stem cells (HSCs) and create a niche for gene-corrected/donor HSCs. Conventional conditioning agents are non-specific, leading to off-target toxicities and resulting in significant morbidity and mortality. We developed tissue-specific anti-human CD45 antibody-drug conjugates (ADCs), using rat IgG2b anti-human CD45 antibody clones YTH24.
View Article and Find Full Text PDFMol Cancer
January 2024
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a "living drug" has achieved hematological malignancy cures with a high response rate, and significant research efforts have been made to facilitate its translation to solid tumors.
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