Cancer immunotherapy with immunoadjuvants, nanoparticles, and checkpoint inhibitors: Recent progress and challenges in treatment and tracking response to immunotherapy

Abstract

Chemotherapy, surgery, and radiation are accepted as the preferred treatment modalities against cancer, but in recent years the use of immunotherapeutic approaches has gained prominence as the fourth treatment modality in cancer patients. In this approach, a patient's innate and adaptive immune systems are activated to achieve clearance of occult cancerous cells. In this review, we discuss the preclinical and clinical immunotherapeutic (e.g., immunoadjuvants (in-situ vaccines, oncolytic viruses, CXC antagonists, device activated agents), organic and inorganic nanoparticles, and checkpoint blockade) that are under investigation for cancer therapy and diagnostics. Additionally, the innovations in imaging of immune cells for tracking therapeutic responses and limitations (e.g., toxicity, inefficient immunomodulation, etc.) are described. Existing data suggest that if immune therapy is optimized, it can be a real and potentially paradigm-shifting cancer treatment frontier.

Keywords: Cancer immunology; Checkpoint inhibitor; Immunoadjuvant; Immunotherapy; Nanoparticles.

Fig. 1.

Pre-clinical or clinical agents in current use for modulation of tumor immune microenvironment.

Fig. 2.

Anti-PD1 (pembrolizumab) therapy induces regression of castration resistant prostate tumors in patients. In patient 10, a significant reduction in the metastatic sites was noted 12-weeks post treatment with anti PD-1 and enzalutamide. Patient 1 also showed significant reduction in tumor size post treatment (Fig. adapted from Graff et al). Reproduced with permissions from Oncotarget, 2016; 7:52810–52817.

Fig. 3.

Tracking infiltration of tumor associated macrophages (TAMs) in murine tumors. A genetically engineered mouse model with bioluminescent TAM was developed. a-c) Upon implantation of ovarian cancer (ID8), a significant enhancement in the TAM infiltration in the peritoneal cavity was noted; d-f) The immunosuppressive ID8 tumors skewed the phenotype of macrophages towards pro-tumoral M2 macrophage. Reprinted with permission from Springer: Springer Nature [Molecular Imaging and Biology] [He et al.] (Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer, Huanhuan He, Alan C. Chiu, Masamitsu Kanada et al), [COPYRIGHT] (2017)