ANTIBODY THERAPY OF MURINE LEUKEMIA TABLE I Relationship of Antibody Dose and Antitumor Effects

The passive serum therapy of exper imenta l and clinical tumors, while f requent ly a t t empted , has met with only very l imi ted success (1). The elegant techniques of K~Jhler and Mils tein (2), enab l ing the produc t ion of vi r tual ly un l imi ted amount s of homogeneous an t ibody, have led to a reconsiderat ion of passive an t ibody t r ea tment for ma l ignan t disease. This interest is based on the possibil i ty that the use of monoclonal ant ibodies may be successful where serum was unsuccessful because (a) insufficient amounts of, or low ti ter serum was used; (b) an t ibody of ineffective isotype(s) was p redominan t ; (c) the an t ibody was of low avidi ty; or (d) the a n t i b o d y was of inappropr i a t e specificity. Monoclona l ant ibodies sui table for t r ea tment would ideal ly be those specifically reactive with tumor cell surfaces. Since the search for true tumor-specif ic an t ibodies has been unsuccessful, an a l ternat ive approach has been taken using an t ibodies that are reactive with mal ignan t and normal cells but that are not lethal or s ignif icant ly toxic to the recipients (3-16). Wi th this approach , we have been able to use monoclona l ant ibodies successfully against a normal mur ine dif ferent ia t ion ant igen for the t reatment of a t r ansp lan ted T cell leukemia. Specifically, monoclonal ant ibodies against the ThyI . 1 different ia t ion ant igen induced pro longed survival and cured a significant propor t ion of t reated animals chal lenged with syngeneic A K R / J SL2 leukemia cells (4). In those studies, a compar ison of ant ibodies of the immunog lobu l in M (IgM), IgG~,, and IgG3 isotypes demons t ra ted that the IgG2~ an t ibody was most effective and the l g M an t ibody ineffective. In the present study, we further examined the a n t i t u m o r act ivi ty of the IgG2a an t i -Thyl .1 monoclonal an t ibody. We found that an t i body therapy could consistently e l iminate up to 3 × l0 s t r ansp lan ted syngeneic SL2 leukemia, and identif ied factors which l imited the effectiveness of an t ibody. Specifically, metas ta t ic disease resulted from the growth of Thy-1.1-negat ive leukemic cells, whereas deve lopment of a solid tumor nodule at the inoculum site resulted from failure of the host to e l iminate anti-Thy-1.1 an t ibody-coa ted tumor cells.