In situ vaccination against a non-immunogenic tumour using intratumoural injections of liposomal interleukin 2.
Cancers appear to escape surveillance by the immune system at least in part because they fail to induce a protective immune response. Therapeutic vaccines based on specific tumour antigens and tumour cells modified ex vivo by genetic techniques are but two strategies being used to circumvent this problem. In this report, we describe a simple, yet effective alternative in which tumour-specific responses are induced by in situ administration of a well-characterized liposomal formulation of the cytokine interleukin 2 (IL-2). Using the non-immunogenic B16 melanoma model, intratumoural injections of liposomal IL-2 L(IL2), were shown to induce a long-lived immune response specific for the injected tumour. In conjunction with subsequent removal of the primary tumours by surgery, the injections increased mean survival to 57 days from a control value of 32 days and partially protected surviving mice against re-challenge with B16. L(IL2) induced an early infiltration of inflammatory cells within the tumours which was followed several days later by an influx of CD3+ T cells. The cellular influx and a coincident decrease in tumour growth were noted in both injected tumours and a second non-injected tumour on the same animal, thereby demonstrating the systemic nature of the immune response. Intratumoural injections of soluble IL-2 at the same dose failed to induce B16-specific cellular immunity or to prolong survival of the mice. Thus, liposomal formulation of the cytokine was fundamental to successful induction of immunity by this in situ vaccination regimen.
Neville
M E
ME
Biomira USA Inc., 1002 Eastpark Blvd, Cranbury, NJ 08512, USA. mneville@biomira.com
Robb
R J
RJ
Popescu
M C
MC
D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D002455:Cell Division; D005260:Female; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D007376:Interleukin-2; D008081:Liposomes; D011994:Recombinant Proteins; D007371:Interferon-gamma