INHIBITION OF IN-VIVO TUMOR-GROWTH BY THE BETA-CHEMOKINE, TCA3

TCA3 is a proinflammatory murine glycoprotein that shares structural f eatures with cytokines of the beta chemokine family and is a chemoattr actant for neutrophils and monocytes. To assess the in vivo functions of TCA3, the cDNA was expressed in two mouse myeloma cell lines. Altho ugh the transfected and control cells had similar growth rates in vitr o, TCA3-expressing tumors demonstrated impaired growth in both normal and immunodeficient mice. Histologic evaluation of the injection sites demonstrated that TCA3 expression resulted in an early neutrophil and monocyte infiltrate accompanied by tumor necrosis. There was complete regression of the TCA3-transfected tumor in some immunocompetent syng eneic mice. The TCA3-transfected cells induced specific and long-lasti ng immunity in mice that showed complete tumor regression; these anima ls were resistant to challenge with nontransfected tumor cells. In con trast, priming with irradiated tumor cells provided little protection against challenge with nontransfected tumor, which indicates that TCA3 specifically augments tumor immunogenicity. Mixing TCA3-transfected c ells with normal tumor cells causes retarded growth of the normal tumo r cells provided the latter are injected into the same site. Furthermo re, direct in situ injection of soluble rTCA3 early during the course of tumor implantation also inhibits tumor growth. The data suggest tha t TCA3 may perform two roles in tumor protection: it induces lymphocyt e-independent antitumor activity and stimulates tumor-specific immunit y. We speculate that TCA3 has natural adjuvant activities that result in augmented immune responses.