Oncotarget Volume 11, Issue 7 reported that although melanoma risk can be minimized with behavioral changes, vaccinating high-risk individuals against melanoma may be the most efficacious preventative method.
Accordingly, using a highly attenuated, double-mutant L. monocytogenes strain expressing a tumor-associated antigen, the researchers obtained significant protection against melanoma in a mouse model.
The Listeria-based vaccine-induced protection through antigen-specific CD8+ T-cells inducing both a protective primary and a memory T-cell response.
In an Oncotarget Research Paper titled "Checkpoint blockade inhibitors enhance the effectiveness of a Listeria monocytogenes-based melanoma vaccine" Dr. Peter H. Dube from the Department of Microbiology, Immunology and Molecular Genetics at The University of Texas Health Science Center said, "The incidence and mortality rates for numerous common human cancers such as breast, cervical, colorectal, lung, ovarian, and prostate have declined over the past fifteen years."
"The incidence and mortality rates for numerous common human cancers such as breast, cervical, colorectal, lung, ovarian, and prostate have declined over the past fifteen years."
- Dr. Peter H. Dube, Department of Microbiology, Immunology and Molecular Genetics at The University of Texas Health Science Center
Conversely, for melanoma over the same time period, incidence rates increased while mortality rates remained unchanged.
Among solid tumors worldwide, the incidence rate for cutaneous melanoma is the fastest growing and three-year survival rates for patients with metastatic melanoma remain at roughly 15%.
The introduction of CPB in the treatment of melanoma is expected to reduce 5-year mortality rates in mice.
However, these recent improvements in metastatic melanoma treatment are not yet curative and will have no effect on melanoma incidence rates.
Figure 1: Attenuated L. monocytogenes expressing TAA induces specific CD8+ T-cell response. (A) Schematic of chicken ovalbumin (OVA) or mouse GP100, both tumor-associated antigens, fused to the first 100 amino acids of a truncated actin-assembly inducing protein (ActA). Along with a mutated phospholipase C (plcB), the introduction of the immunodominant epitope of OVA (AAs 257-265), create the OVA-expressing L. monocytogenes vaccine strain (Lm: OVA). Female (left panel) and male (middle panel) mice vaccinated with 2 × 104 CFU of Lm: OVA develop OVA specific CD8+ (B) and TCRβ+ (C) cells compared to mice receiving the Lm: Parental vaccine (ΔactA: plcB), right panel. (D) Survival of mice (n = 4 per group) receiving 2 × 107 CFU of either L. monocytogenes strain 10403S (black), Lm: Parental (red) Lm: OVA (green), or Lm: GP100 (blue). Statistical analysis was performed as a Mantel-Cox Log-rank test (p = 0.0074).
For these reasons, an effective melanoma vaccine is likely to be the most effective means to reduce incidence rates in these specific individuals.
Therapeutic cancer vaccines have been elusive, but the properties of Lm that make it a good preventative vaccine could also be beneficial as a therapeutic vaccine.
The Dube Research Team concluded, in their Oncotarget research paper, that although their data provide substantial evidence that Lm-based vaccines are efficient preventative vaccines, they did not evaluate the potential of this vaccine under therapeutic conditions.
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Full text - https://doi.org/10.18632/oncotarget.27490
Correspondence to - Peter H. Dube - [email protected]
Keywords - cancer immunotherapy, cancer vaccination, checkpoint blockade, melanoma, listeria
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