Vaccine Therapy in Non-Small Cell Lung Cancer

Abstract

Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes. Therapeutic cancer vaccines are designed to exploit the body’s immune system to activate long-lasting memory against tumor cells that ensure tumor regression, with minimal toxicity. A unique feature of cancer vaccines lies in their complementary approach to boost antitumor immunity that could potentially act synergistically with immune checkpoint inhibitors (ICIs). However, single-line immunization against tumor epitopes with vaccine-based therapeutics has been disappointingly unsuccessful, to date, in lung cancer. The high level of success of several recent vaccines against SARS-CoV-2 has highlighted the evolving advances in science and technology in the vaccines field, raising hope that this strategy can be successfully applied to cancer treatments. In this review, we describe the biology behind the cancer vaccines, and discuss current evidence for the different types of therapeutic cancer vaccines in NSCLC, including their mechanisms of action, current clinical development, and future strategies.

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“…Part 2 is now ongoing and will enroll 363 participants with OS as the primary endpoint (NCT02654587). Personalized antigen vaccination is constructed by whole exome and RNA sequencing of the tumour and identification of personalized immunogenic neoepitopes based on bioinformatic algorithms ( 164 ). In a phase Ib study, response rate was 39% with no extra safety signals reported in 18 patients in the NSCLC cohort who received NEO-PV-01 (a personalized neoantigen vaccine) concurrently with nivolumab ( 165 ).…”

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“…For example, many TAAs are monomorphic self-antigens, which are expressed in both cancer cells and normal host cells. TSAs (neoantigens) are encoded by tumor-specific somatic mutations and are particularly expressed in neoplastic cells [ 30 ].…”

“…In contrast to TAAs, TSAs are less likely affected by central or peripheral tolerance due to molecular alterations [ 32 , 33 ]. TSAs are easily generated because of the genomic instability presented in lung cancer, and are effectively identified by immune system of the host [ 30 ]. Thus, the generation of TSAs will contribute to designing tumor vaccines, such as identification of TSAs by rapid genomic profiling and computational prediction pipelines based on next-generation sequencing [ 33 ].…”

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“…They are usually highly immunogenic as they are not expressed in normal tissues [ 1 ]. Neoantigens play an increasingly important role in immunotherapy [ 2 , 3 , 4 ], and in particular they are used in the design of vaccines aimed to fight several types of cancer, such as kidney cancer [ 5 ], glioblastoma [ 6 ], non-small cell lung cancer [ 7 ], pancreatic cancer [ 8 ], hepatocellular carcinoma [ 9 ], colon cancer [ 10 ], esophageal cancer [ 11 ], or breast cancer [ 12 ].…”