Comparison of combinations of interferons with tumor specific and nonspecific monoclonal antibodies as therapy for murine B- and T-cell lymphomas.
Two murine models, C3H 38C13 B-cell lymphoma and AKR SL2 T-cell lymphoma were used to determine the efficacy of three different interferon preparations, recombinant human hybrid interferon-alpha A/D, recombinant murine interferon (rMIFN)-gamma, and natural MIFN-alpha/beta (greater than or equal to 85% beta), alone and in combination with tumor specific and nonspecific monoclonal antibody therapy. All three interferon preparations have direct in vitro antigrowth activity for 38C13 and SL2. All three interferons have direct antitumor activity in vivo for 38C13 lymphoma at high doses; however, none of these interferons has independent antitumor activity for SL2 in vivo. These data indicate that there is no relationship between in vitro growth cytostasis/cytolysis and in vivo antitumor response. All three interferon preparations will potentiate both tumor specific and nonspecific monoclonal antibody therapy. Natural MIFN-alpha/beta and recombinant human hybrid interferon-alpha A/D, which should share a common cell surface receptor, had similar antitumor activity in both models. Combining recombinant human hybrid interferon-alpha A/D and rMIFN-gamma therapy was not additive for 38C13 lymphoma and a three-way combination with antiidiotype was not significantly more effective than combination therapy with one interferon type. In general, rMIFN-gamma was more effective in in vivo combination therapy against the s.c. T-cell lymphoma than against the i.p. B-cell lymphoma and was more synergistic with anti-Thy1.1 than with antiidiotype.
Basham
T Y
TY
Division of Infectious Diseases, Stanford University School of Medicine, California 94305.
Palladino
M A
MA
Badger
C C
CC
Bernstein
I D
ID
Levy
R
R
Merigan
T C
TC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001402:B-Lymphocytes; D007372:Interferons / Q000008:administration & dosage* / Q000627:therapeutic use; D008223:Lymphoma / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D007372:Interferons