Surface exposed
phosphatidylserine (PS) of
cancer aids it to evade immune surveillance and thereby results in
tumor progression. Earlier, we reported that PS targeting cationic
liposomes,
phosphatidylcholine-
stearylamine (PC-SA), alone and in combination with doxorubicin can result
in complete remission of B16F10
melanoma in C57BL/6 mice without signs of toxicity. Inducing an immunogenic response is highly crucial for any
cancer therapy as it is essential in improving the tumor microenvironment for any
drug to act. Herein, we demonstrate that PC-SA, besides having
tumor reducing ability, elicits a strong immune response. The combination
therapy (PC-SA-DOX) is superior to free DOX in enhancing the anti-
tumor immune effect on CD4-positive and CD8-positive T cells for IFN-γ,
IL-2 and TNF-α production in sera and splenic culture supernatants of B16F10
tumor-induced mice. An upregulation of
IL-12 and NO production is evidenced in spleen cultures of these mice, thereby showing a promising role of both Th1 type and innate immune response for host anti-
tumor activity. Complete elimination of
cancer is sometimes accomplished by surgery, but its effectiveness is often limited due to the propensity of
cancers to spread to distant organs by
metastasis. In our present study, we show that in PC-SA-DOX treated mice, the elevated Th1
cytokine levels create an immuno-protective environment which thereby facilitates in curing lung
metastasis. Our results, therefore, warrant the need of effective immune stimulation by anticancer formulations for inhibition of solid
tumors and
metastasis, demonstrated by the liposomal DOX formulation.