Effect of tumor-associated antigens on specific T-cell responses in patients with metastatic lung cancer and potential use as immunogenic targets for a (polyvalent) vaccination strategy.

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host’s cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

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GTL001 and bivalent CyaA-based therapeutic vaccine strategies against human papillomavirus and other tumor-associated antigens induce effector and memory T-cell responses that inhibit tumor growth

Vaccine ◽

10.1016/j.vaccine.2017.01.074 ◽

2017 ◽

Vol 35 (11) ◽

pp. 1509-1516 ◽

Cited By ~ 2

Author(s):

Michaël Esquerré ◽

Marie Momot ◽

Anne Goubier ◽

Christophe Gonindard ◽

Stéphane Leung-Theung-Long ◽

...

Keyword(s):

Human Papillomavirus ◽

T Cell ◽

Tumor Growth ◽

Therapeutic Vaccine ◽

T Cell Responses ◽

Inhibit Tumor Growth ◽

Memory T Cell ◽

Tumor Associated Antigens ◽

Cell Responses

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Enhanced T Cell Responses Induced by a Necrotic Dendritic Cell Vaccine, Expressing HCV NS3

Frontiers in Microbiology ◽

10.3389/fmicb.2020.559105 ◽

2020 ◽

Vol 11 ◽

Author(s):

Zelalem A. Mekonnen ◽

Makutiro G. Masavuli ◽

Wenbo Yu ◽

Jason Gummow ◽

Dawn M. Whelan ◽

...

Keyword(s):

T Cell ◽

Vaccination Strategy ◽

T Cell Responses ◽

Dendritic Cell Vaccine ◽

Effector Memory ◽

Cell Vaccine ◽

Cell Mediated Immunity ◽

Structural Protein ◽

Cell Responses ◽

Dc Vaccine

A vaccine that induces potent, broad and sustained cell-mediated immunity, resulting in effective memory has the potential to restrict hepatitis C (HCV) virus infection. Early, multi-functional CD4+ and CD8+ T cell responses against non-structural protein 3 (NS3) have been associated with HCV clearance. Necrotic cells generate strong immune responses and represent a major antigenic source used by dendritic cells (DC) for processing and presentation, but there is conflicting evidence as to their immunogenicity in vaccination. Immunization with DC loaded with viral antigens has been done in the past, but to date the immunogenicity of live vs. necrotic DC vaccines has not been investigated. We developed a DC2.4 cell line stably expressing HCV NS3, and compared the NS3-specific responses of live vs. necrotic NS3 DC. Vaccination of mice with necrotic NS3 DC increased the breadth of T-cell responses and enhanced the production of IL-2, TNF-α, and IFN-γ by effector memory CD4+ and CD8+T cells, compared to mice vaccinated with live NS3 DC. A single dose of necrotic NS3 DC vaccine induced a greater influx and activation of cross-presenting CD11c+ CD8α+ DC and necrosis-sensing Clec9A+ DC in the draining lymph nodes. Furthermore, using a hydrodynamic challenge model necrotic NS3 DC vaccination resulted in enhanced clearance of NS3-positive hepatocytes from the livers of vaccinated mice. Taken together, the data demonstrate that necrotic DC represent a novel and exciting vaccination strategy capable of inducing broad and multifunctional T cell memory.

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Circulating Interleukin-4 Is Associated with a Systemic T Cell Response against Tumor-Associated Antigens in Treatment-Naïve Patients with Resectable Non-Small-Cell Lung Cancer

Cancers ◽

10.3390/cancers12123496 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3496

Author(s):

Seyer Safi ◽

Yoshikane Yamauchi ◽

Hans Hoffmann ◽

Wilko Weichert ◽

Philipp J. Jost ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

T Cell ◽

T Cell Responses ◽

Small Cell ◽

Small Cell Lung ◽

Cell Responses ◽

Tumor Tissues ◽

Cytokine Levels ◽

Treatment Naïve

Spontaneous T cell responses to tumor-associated antigens (TAs) in the peripheral blood of patients with non-small-cell lung cancer (NSCLC) may be relevant for postoperative survival. However, the conditions underlying these T cell responses remain unclear. We quantified the levels of 27 cytokines in the peripheral blood and tumor tissues from treatment-naïve patients with NSCLC (n = 36) and analyzed associations between local and systemic cytokine profiles and both TA-specific T cell responses and clinical parameters. We defined T cell responders as patients with circulating T cells that were reactive to TAs and T cell nonresponders as patients without detectable TA-specific T cells. TA-specific T cell responses were correlated with serum cytokine levels, particularly the levels of interleukin(IL)-4 and granulocyte colony-stimulating factor (G-CSF), but poorly correlated with the cytokine levels in tumor tissues. Nonresponders showed significantly higher serum IL-4 levels than responders (p = 0.03); the predicted probability of being a responder was higher for individuals with low serum IL-4 levels. In multivariable Cox regression analyses, in addition to IL-4 (hazard ratio (HR) 2.8 (95% confidence interval (CI): 0.78–9.9); p = 0.116), the age-adjusted IL-8 level (HR 3.9 (95% CI: 1.05–14.5); p = 0.042) predicted tumor recurrence. However, this study included data for many cytokines without adjustment for multiple testing; thus, the observed differences in IL-4 or IL-8 levels might be incidental findings. Therefore, additional studies are necessary to confirm these results.

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