A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.
Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
E
E
Hu
A L
AL
Epstein
G S
GS
Naeve
I
I
Gill
S
S
Martin
A
A
Sherrod
P
P
Nichols
D
D
Chen
A
A
Mazumder
A M
AM
Levine
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes; D003602:Cytotoxicity, Immunologic; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000032:analysis; D007958:Leukocyte Count; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D007136:Immunoglobulins