Human mouse chimeric CD7 monoclonal antibody (SDZCHH380) for the prophylaxis of kidney transplant rejection.
mAb directed against CD7 have been shown to inhibit T cell proliferation in the allogeneic mixed lymphocyte reaction suggesting that CD7 may be an appropriate target for in vivo immunotherapy. We performed a prospective randomized clinical trial with a human-mouse chimeric CD7 mAb (SDZCHH380) and compared it with murine OKT3 for the prophylaxis of kidney transplant rejection. Twenty recipients of first cadaveric renal allografts were randomized to receive either SDZCHH380 or OKT3. SDZCHH380 was well tolerated. Rejection was delayed to day 35. No patients were sensitized to SDZCHH380. In contrast 7/10 OKT3 patients made anti-OKT3 antibodies. SDZCHH380 coated peripheral blood and lymph node T cells and, in contrast to OKT3, induced minimal release of IL-2, IL-6, TNF-alpha, and IFN-gamma. In addition, we showed that CD7-negative T cells mediated rejection in one of the SDZCHH380-treated patients. We conclude that the human-mouse chimeric CD7 mAb SDZCHH380 is well tolerated, is not immunogenic, and merits further study in the prophylaxis of transplant rejection.
Lazarovits
A I
AI
Multi-Organ Transplant Service, University Hospital, London, Ontario, Canada.
Rochon
J
J
Banks
L
L
Hollomby
D J
DJ
Muirhead
N
N
Jevnikar
A M
AM
White
M J
MJ
Amlot
P L
PL
Beauregard-Zollinger
L
L
Stiller
C R
CR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D011993:Recombinant Fusion Proteins