Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.
BACKGROUND
Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer.


METHODS
Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up.


RESULTS
Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%.


CONCLUSIONS
The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies.


BACKGROUND
UMIN UMIN000001835.
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan ; Department of Cancer ImmunoCell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Takeshi
T
Ishikawa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan ; Department of Cancer ImmunoCell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Satoshi
S
Kokura
Center for Cell and Gene Therapy, Takara Bio Inc, Otsu, Japan.
Tatsuji
T
Enoki
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Naoyuki
N
Sakamoto
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan ; Department of Cancer ImmunoCell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tetsuya
T
Okayama
Center for Cell and Gene Therapy, Takara Bio Inc, Otsu, Japan.
Mitsuko
M
Ideno
Center for Cell and Gene Therapy, Takara Bio Inc, Otsu, Japan.
Junichi
J
Mineno
Division of Basic Research, Louis Pasteur Center for Medical Research, Kyoto, Japan.
Kazuko
K
Uno
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Naohisa
N
Yoshida
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuhiro
K
Kamada
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuhiro
K
Katada
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kazuhiko
K
Uchiyama
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Osamu
O
Handa
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tomohisa
T
Takagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Hideyuki
H
Konishi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Nobuaki
N
Yagi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yuji
Y
Naito
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshito
Y
Itoh
Department of Cancer ImmunoCell Regulation, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Toshikazu
T
Yoshikawa
D000328:Adult; D000368:Aged; D000855:Anorexia / Q000209:etiology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005221:Fatigue / Q000209:etiology; D005260:Female; D005353:Fibronectins / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011994:Recombinant Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013921:Thrombocytopenia / Q000209:etiology; D016896:Treatment Outcome; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
D018106:CD28 Antigens; D016207:Cytokines; D005353:Fibronectins; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C545354:retronectin; D017493:Leukocyte Common Antigens