ABSTRACT
Immunostimulatory monoclonal antibodies (IS-mAb) have been proven to enhance the therapeutic effectiveness of various anticancer therapy. In the present investigation, we launched a separate combinational therapy for the treatment of triple-negative breast cancer (TNBC) using cuttlefish ink-based nanoparticles (CINPs) for photothermal therapy (PTT) and anti-OX40 antibody. Our goal was to increase the therapeutic response to the disease. CINPs were characterized by their physicochemical properties, which revealed that they had a hydrodynamic diameter ranging from 128 to 148 nm, a negative surface charge, and a high photothermal conversion efficiency under both in vitro and in vivo settings. In TNBC model, we evaluated the therapeutic effectiveness of the following groups: CINP-PTT + anti-OX40 Ab (G1), CINPs-PTT (G2), CINPs + anti-OX40 Ab (G3), anti-OX40 (G4) or PBS (G5). In each case, we assessed the efficacy of these groups against one another. The intratumor administration of all of the substances and therapies was performed. CINP-PTT + anti-OX40 Ab and CINP + anti-OX40 Ab (particularly CINP-PTT + anti-OX40 Ab) induced significant tumor regression in treated (breast) and non-treated (flank) tumor, and completely inhibited lung metastasis, thereby inducing a higher survival rate in mice in comparison to CINP-PTT, anti-OX40 Ab, or PBS. This was the case because in CINPs-treated tumors, particularly those treated with CINPs-PTT, intratumoral injection of CINPs increased the frequency of OX40, CD8 double-positive T cells. CINPs improved the conversion of the macrophage phenotype from M2 to M1 in vitro, which is significant from an immunological point of view. In addition, anti-OX40 Ab combined with CINPs or, more specifically, CINPs-PPT produced a larger frequency of preexisting and newly formed tumor-specific CD8 T cells, as well as an enhanced frequency of CD8 T cells infiltrating non-treated tumors, in comparison to respective monotherapies. When the data were taken into consideration as a whole, it seemed that CINPs-based PTT may effectively enhance the antitumor response effectiveness of anti-OX40 Ab.
