Immunization with Chemically Modified Lymphoma Cells¹

Although 6C3HED ascites lymphosarcoma grows lethally in C3H mice at low tumor cell inoculum, potent immune responses to this tumor have been elicited. It was selected as a model for studying the effectiveness of a number of chemical modifications of the tumor in eliciting immune responses of sufficient potency to protect the animal against a challenging lethal dose of the tumor cells. 6C3HED cells were modified by reactions with: (a) diazotized p-aminobenzoic acid, (b) fluorodinitrobenzene, (c) iodoacetamide, (d) iodoacetate, (e) N-ethylmaleimide, and (f) p-hydroxymercuribenzoate. Cells modified with the strong antigenic determinants a and b failed to protect against 10⁶ 6C3HED cells; c, d, and e protected fully; f gave partial protection. Alterations producing potent immunity involved blocking sulfhydryl groups with reagents not generally considered good haptens. Iodoacetamide-treated EPF-1 lymphoma protected against an early transplant generation of EPF-1. No cytotoxic antibody to 6C3HED or EPF-1 in immune serum was demonstrable, but lymphoid cells from an immune C3H mouse protected a susceptible animal, indicating cell-mediated immunity.