Combination of low‐dose cisplatin and recombinant xenogeneic endoglin as a vaccine induces synergistic antitumor activities

Abstract

Angiogenesis is critical to the growth and metastasis of solid tumors, and acquired drug resistance is one of the major hindrances to chemotherapy. Thus, we sought a rational strategy using the combination of antiangiogenic biotherapy and chemotherapy for cancer therapy. We explored the efficacy of a strategy combining low-dose cisplatin and a recombinant xenogeneic endoglin as a protein vaccine, which we previously demonstrated to have effective antiangiogenic effects in several mouse models. We found that both lowdosage cisplatin and xenogeneic endoglin vaccine individually resulted in effective suppression of tumor growth in 2 tumor models via inhibition of tumor angiogenesis. Remarkably, the combination therapy resulted in not only significant antiangiogenic effects but also additional promotion of tumor cell apoptosis and inhibition of tumor cell proliferation, without any ensuing increase in host toxicity during the course of treatment, which lasted for 6 months. In addition, the combination demonstrated a synergistic relationship, which was shown in all of the synergistic indexes, i.e., tumor volume, angiogenesis, apoptosis and proliferation. Both antibodies and antibody-producing B cells against mouse self-endoglin were observed in all mice immunized by the xenogeneic endoglin vaccine (alone and combination), which suggested that low-dose cisplatin did not suppress the host immune response but potentiated the antitumor activity of the xenogeneic endoglin vaccine. These observations may provide the basis for an effective alternative strategy for cancer therapy in the near future.

Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma

“…After tumors had grown for 7 days, the mice were randomly divided into four groups (10 mice/group) for treatments according to similarly described procedures. 42 . At the end of the experiment, the mice were killed and their tumor tissues were collected for subsequent histological experiments (see below).…”

“…Digital images were acquired and processed using Adobe Photoshop (Adobe Inc., Mountain View, CA, USA), and were quantified as described previously. 42 …”

Low-Dose Paclitaxel Prior to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth

“…Several recent studies comparing the efficacy of chemotherapy at high and low doses in combination with antiangiogenic drug documented the longest survival in animals that received low-dose chemotherapy and antiangiogenic treatment. This was associated with no side effects and a marked decrease in tumor size (19)(20)(21). However, there are no reports that address the therapeutic and immunomodulating potential of lowdose chemotherapeutic agents in a setting of combined chemotherapy with cancer vaccines.…”

Volumetric and Angiogenic Evaluation of Antitumor Effects with Acoustic Liposome and High-Frequency Ultrasound

“…The main function of CDDP is to damage DNA and induce apoptosis (24,25). Although CDDP is not thought to inhibit angiogenesis specifically, some researchers have reported that CDDP provided antiangiogenic effects against several human and mouse cancer cells, including Colon26 carcinoma (26,27). In addition, the larger vessels in the outer area of tumor are less affected by the antiangiogenic therapy, but small vessels perfused in the tumor are more sensitive to the therapy (1,28,29).…”