Blood, 1 March 2002, Vol. 99, No. 5, pp. 1503-1504
"Special delivery" to cancer cells
Despite 20 years of clinical trials, systemically administered
interleukin-2 (IL-2) induces clinical responses in only a very small
minority of patients with only a few types of cancer. Based on the
assumption that the results are limited largely by inadequate concentrations of IL-2 at the tumor sites and by the toxicity of high
dose IL-2, approaches are being explored to deliver IL-2 preferentially or specifically to the tumor.
Carnemolla and colleagues (page 1659) have devised a novel delivery
system, namely, a fusion protein between IL-2 and a human antibody
(L19) directed against an extracellular matrix (ECM) component
of newly forming tumor blood vessels. In this study, the fusion protein
(L19-IL-2) administered to tumor-bearing mice selectively delivered
IL-2 to the tumor vessels and exerted a significant antitumor effect.
The localization to the tumor vessels suggests applicability to
"solid" tumors, and even to hematologic malignancies, forming new
blood vessels.
IL-2 is not directly cytotoxic and the mechanism for its antitumor
effect
whether via T cells, NK cells, or other cytokinesdiffers for
different cancers. Therefore, the clinical therapeutic effect of IL-2
delivered by L19-IL-2 might be restricted to those cancers known to respond to systemic IL-2 or the increased IL-2 concentration at the tumor site might exert an antitumor effect on cancers not known to respond to systemic IL-2. The former possibility would improve
the therapeutic index, while the latter would represent a major advance
in cancer therapy.
Angiogenesis-associated ECM components represent pan-tumor
antigens, which can serve as targets for the delivery of a
variety of immunostimulatory or cytotoxic molecules, for example,
GM-CSF or IL-12, or toxins or radiation, for
example, I131 or Y90, selectively to tumor
sites for greater antitumor activity and less toxicity. This
study represents one such exciting approach.
Alexander Fefer
University of Washington
