Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD

Abstract

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day ؉56. Eight patients experienced grades II to IV acute graft-versushost disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A*0201 pentamer in 6 patients with CRC. CEA-specific CD8 ؉ T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEAspecific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response.

H-2Kb–Restricted CTL Epitopes from Mouse Heparanase Elicit an Antitumor Immune Response In vivo

“…At present, identification of TAAs in cancer patients has been limited to a few cancers, such as MART-1 (melanoma antigen recognized by T cell-1), which is specific for melanoma (30), and carcinoembryonic antigen, which is specific for gastrointestinal tumors (22,31). These tumor-specific antigens, also called autoantigens, are shared among patients with the same type of tumor.…”

Alternative BCR/ABL Splice Variants in Philadelphia Chromosome–Positive Leukemias Result in Novel Tumor-Specific Fusion Proteins that May Represent Potential Targets for Immunotherapy Approaches

“…CD8 + cells were positively purified from PBMCs using magnetically labeled mAb to CD8 (Miltenyi). Dendritic cells were generated from PBMCs as already described, with slight modifications (30). Briefly, CD14 + cells were positively purified with magnetically labeled mAb to CD14 and cultured with granulocyte macrophage colony-stimulating factor (GM-CSF; 80 ng/mL) and IL-4 (40 ng/mL) for 40 h. A cocktail of proinflammatory cytokines was then added for additional 24 h [GM-CSF, 80 ng/mL; IL-4, 40 ng/mL; IL-6, 10 ng/mL; IL1-h, 10 ng/mL; tumor necrosis factor-a (TNF-a), 20 ng/mL; and prostaglandin E 2 (PGE 2 ), 10 Amol/L; GM-CSF, IL-4, IL1-h IL-6, and TNF-a were from Peprotech; PGE 2 was from Alexis Biochemicals].…”

Poor prognosis osteosarcoma: new therapeutic approach

“…[15][16][17][18] We reported the evidence of metastases regression in a 12-year-old boy with advanced osteosarcoma, in which the immunological anti-osteosarcoma effect was independent of the GvHD reaction. 17 Goi et al 19 treated a nine-year-old boy with metastatic disease with reduced intensity transplantation.…”