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Fulltext Immunotherapy for head and neck cancer

Sok Ching Cheong

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):5-5.
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Head and neck cancers have been reported to have high immune infiltration scores, and clinical benefits of the anti-PD1 checkpoint inhibitor have been demonstrated in recurrent and metastatic cancers. Recent genetic signa-tures of the immune compartment have provided insights to delineate immune-active and -exhausted subtypes, to understand the immune status of OSCC patients that could further drive the development of novel immunotherapies. Vaccination with tumour-associated antigens is an approach to improve tumour recognition which could result in the eradication of cancer cells. Here, I would describe our efforts in developing antigen-specific vaccines for head and neck cancer. Using the B6.Cg-Tg(HLA-A/H2-D)2Enge/J mice bearing established tumours overexpressing the tumour antigens, we demonstrated that the vaccine delayed tumour growth, and in combination with anti-PD1, completely eliminated the tumour. The vaccine increased the expression of PD1 in T cells, and vaccinated animals showed increased antigen-specific responses by the ELISPOT assay. In summary, our data show that antigen-specific vaccine works synergistically with anti-PD1 and could be a promising therapeutic agent for head and neck cancer.

Matched MeSH terms: Enzyme-Linked Immunospot Assay
Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy

Leng CY, Low HC, Chua LL, Chong ML, Sulaiman H, Azwa I, et al.

HIV Med, 2017 05;18(5):321-331.
PMID: 27649852 DOI: 10.1111/hiv.12432

OBJECTIVES: Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.
METHODS: Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells.
RESULTS: HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses.
CONCLUSIONS: HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%).

Matched MeSH terms: Enzyme-Linked Immunospot Assay
Fulltext Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

Chai SJ, Yap YY, Foo YC, Yap LF, Ponniah S, Teo SH, et al.

PLoS One, 2015;10(11):e0130464.
PMID: 26536470 DOI: 10.1371/journal.pone.0130464

Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.

Matched MeSH terms: Enzyme-Linked Immunospot Assay

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