Phase I Trial of Adoptive Cell Transfer with Mixed-Profile Type-I/Type-II Allogeneic T Cells for Metastatic Breast Cancer

• Published in: Clinical cancer research 2011-11, Vol.17 (21), p.6878-6887
• Main Authors: HARDY, Nancy M, MOSSOBA, Miriam E, LEVINE, Bruce L, JUNE, Carl H, KHUU, Hahn M, CARPENTER, Ashley E, KRUMLAUF, Michael C, DWYER, Andrew J, GRESS, Ronald E, FOWLER, Daniel H, BISHOP, Michael R, STEINBERG, Seth M, FELLOWES, Vicki, YAN, Xiao-Yi, HAKIM, Frances T, BABB, Rebecca R, AVILA, Daniele, GEA-BANACLOCHE, Juan, SPORTES, Claude
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Breast Neoplasms - therapy; Female; Graft vs Tumor Effect - immunology; Gynecology. Andrology. Obstetrics; Humans; Immunotherapy, Adoptive - methods; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Stem Cell Transplantation; T-Lymphocytes - immunology; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-11-1579

Metastatic breast cancer (MBC) response to allogeneic lymphocytes requires donor T-cell engraftment and is limited by graft-versus-host disease (GVHD). In mice, type-II-polarized T cells promote engraftment and modulate GVHD, whereas type-I-polarized T cells mediate more potent graft-versus-tumor (GVT) effects. This phase I translational study evaluated adoptive transfer of ex vivo costimulated type-I/type-II (T1/T2) donor T cells with T-cell-depleted (TCD) allogeneic stem cell transplantation (AlloSCT) for MBC. Patients had received anthracycline, taxane, and antibody therapies, and been treated for metastatic disease and a human leukocyte antigen (HLA)-identical-sibling donor. Donor lymphocytes were costimulated ex vivo with anti-CD3/anti-CD28 antibody-coated magnetic beads in interleukin (IL)-2/IL-4-supplemented media. Patients received reduced intensity conditioning, donor stem cells and T1/T2 cells, and monitoring for toxicity, engraftment, GVHD, and tumor response; results were compared with historical controls, identically treated except for T1/T2 product infusions. Mixed type-I/type-II CD4(+) T cells predominated in T1/T2 products. Nine patients received T1/T2 cells at dose level 1 (5 × 10(6) cells/kg). T-cell donor chimerism reached 100% by a median of 28 days. Seven (78%) developed acute GVHD. At day +28, five patients had partial responses (56%) and none had MBC progression; thereafter, two patients had continued responses. Donor T-cell engraftment and tumor responses appeared faster than in historical controls, but GVHD rates were similar and responders progressed early, often following treatment of acute GVHD. Allogeneic T1/T2 cells were safely infused with TCD-AlloSCT, appeared to promote donor engraftment, and may have contributed to transient early tumor responses.