China
Africa
Explore chapters and articles related to this topic
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
There are currently no experimental prophylactic cancer vaccines for primary prevention in Phase III or Phase IV clinical trials, although one of the Phase I clinical trials is investigating the potential use of a Mucin 1 (MUC1) Peptide-Poly-ICLC vaccine in preventing lung cancer in smokers (including former smokers) at high risk of developing this disease. However, the potential introduction of such a vaccine into routine clinical practice has drawn criticism, as it might encourage smokers to continue with their habit if they think the vaccine has lowered their risk, thus perpetuating other smoking-related health problems.
Recent Advances In HIV/AIDS
Published in Anne George, K. S. Joshy, Mathew Sebastian, Oluwatobi Samuel Oluwafemi, Sabu Thomas, Holistic Approaches to Infectious Diseases, 2017
A vaccine candidate targeting dendritic cells in the lymph nodes and other organs of the immune system is under trial. The vaccine candidate contains a monoclonal antibody (mAb) engineered to recognize DEC-205, an endocytic protein found on the surface of dendritic cells that mediates efficient presentation of antigens. The mAb was fused to an HIV clade B p24 Gag protein. Gag p24 was selected as the vaccine antigen because of its many conserved epitopes, which can induce greater breadth of CD8+ T-cell responses. The vaccine candidate was administered in 45 healthy HIV-uninfected individuals with an adjuvant, Poly ICLC (Hiltonol). The adjuvant was used to activate innate immune responses or to help immature dendritic cells. The study was conducted in Rockefeller University in New York (McEnery, 2010).
Targeting macrophages: a novel avenue for cancer drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Sahana Kumar, Anujan Ramesh, Ashish Kulkarni
Toll-like receptors (TLRs) that are expressed on leukocytes like macrophages and dendritic cells recognize pathogen-derived molecules and damaged cell products and induce inflammatory responses [66]. Targeting TLRs in macrophages can hence induce a pro-inflammatory phenotype and potentially enhance anti-tumor efficacy [67,68]. Several preclinical studies using TLR agonists targeting different TLRs like TLR3, TLR7/8, and TLR 9 have shown to polarize macrophages into a more Th1 and M1 like phenotype and reducing tumor progression [69–73]. Polyinosinic-polycytidylic acid (Poly ICLC), a double-stranded RNA that is a ligand for TLR 3 is being evaluated in Phase 1/2 clinical studies for various solid tumors (NCT03262103, NCT03721679, NCT01984892) [74]. TLR7 agonists imiquimod and 852A have been evaluated in clinical trials for various cancers and demonstrated good tolerance and potential anti-tumor capacity (NCT00899574, NCT00319748, NCT00095160, NCT00189332, NCT00091689) [75]. The current clinical studies targeting TAMs to improve anti-cancer efficacy have been summarized in Figure 1.
Enhancing the immune stimulatory effects of cetuximab therapy through TLR3 signalling in Epstein-Barr virus (EBV) positive nasopharyngeal carcinoma
Published in OncoImmunology, 2018
Louise Soo Yee Tan, Benjamin Wong, Nagaraja Rao Gangodu, Andrea Zhe Ern Lee, Anthony Kian Fong Liou, Kwok Seng Loh, Hao Li, Ming Yann Lim, Andres M. Salazar, Chwee Ming Lim
TLR3 agonists are potent immune adjuvants in inducing innate immunity and subsequently amplifying the adaptive immune responses.12 As such, Poly-ICLC has been developed to boost anti-tumor effects; primarily as a vaccine adjuvant in both brain and ovarian malignancies.21–23 Clinical trials using Poly-ICLC have shown it to be safe and well-tolerated in these patients, without significant adverse side effects.24 Although initially thought to induce primarily the innate immune-stimulatory effects via polarizing the Th1-cytokine secretion such as IFN-γ, subsequent studies have also shown further consequential increase in adaptive anti-tumor immune responses.12 The use of Poly-ICLC has been investigated in combination with monoclonal antibody such as cetuximab, a IgG1 antibody targeting the EGFR, in head and neck squamous cell carcinoma (HNSCC).12 This study demonstrated enhanced NK-mediated antibody dependent cellular cytotoxicity (ADCC) with Poly-ICLC in combination; which resulted in increased in EGFR-specific CD8 + T cells. In EBV induced NPC, there is intense inflammatory infiltrates demonstrated in the tumor microenvironment. This observation; coupled with the high expression of EGFR seen in NPC; and with a phase II clinical trial demonstrating good clinical results with cetuximab in NPC; motivated this study to investigate the immune-stimulatory effects of Poly-ICLC in combination with cetuximab in NPC.
Neoantigen vaccine platforms in clinical development: understanding the future of personalized immunotherapy
Published in Expert Opinion on Investigational Drugs, 2021
Suangson Supabphol, Lijin Li, S. Peter Goedegebuure, William E. Gillanders
Administration of synthetic peptides without adjuvant does not trigger toll-like receptors (TLR) or activate the innate immune system. Failure to active ate the innate immune system can lead to attenuated or very weak T cell responses. Thus, immune adjuvants need to be co-administered with peptide vaccines in order to induce robust immune responses [41]. Modern adjuvants include ligands for pattern recognition receptors (PRR), which target the APCs and consequently enhance the adaptive immune response by inducing the production of cytokines and chemokines that play a key role in T cell recruitment, priming, expansion and polarization. These adjuvants interact with and signal through specific receptors, providing a danger signal to the immune system which leads to the activation of transcription factors such NF-κB and IRF. One FDA-approved immune adjuvant is polyinosinic-polycytidylic acid-poly-L-lysine (poly-ICLC). As a double-stranded RNA complex, poly-ICLC is similar in structure to RNA viruses, and can be recognized by endosomal receptor TLR3 and cytoplasmic sensors MDA-5 and DHX/DDX RNA helicases [42]. Other immune adjuvants including cyclic dinucleotide (CDN), a potent stimulator of interferon genes (STING) agonist [43], have also been tested. Peptide vaccines are typically delivered via subcutaneous or intramuscular administration near draining lymph nodes [44] with a typical dose range of 300–450 μg per epitope [45–49]. Insights into better SLP vaccine strategies (dosing, frequency, adjuvant, administration, ?etc.?) are typically derived from animal studies and further refined in clinical trials. Despite some efforts [50], there is still a lack of systemic comparison of different vaccine regimens for optimal immune response and/or antitumor activity. Furthermore, the potential impact of concomitant therapies (chemotherapy, radiation therapy, and immunotherapy) on the effectiveness of SLP vaccines is not fully understood. The trend in the field is to adopt an SLP vaccine strategy with more frequent but decreased doses of vaccine as supported by computational simulation modeling [51].