Personal Neoantigens From Patients With NSCLC Induce Efficient Antitumor Responses

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide.
• Developing effective personalized treatments is crucial for improving patient outcomes.
• Neoantigens, arising from tumor-specific mutations, present a promising target for cancer immunotherapy.

Purpose of the Study:

• To develop a neoantigen-targeted personalized cancer treatment for NSCLC.
• To assess the utility of neoantigens and neoantigen-reactive T cells (NRTs) in NSCLC.
• To validate the immunogenicity and anti-tumor efficacy of selected neoantigens.

Main Methods:

• Whole-exome sequencing of tumor specimens from three NSCLC patients to predict neoantigens.
• Isolation and stimulation of NRTs, followed by IFN-γ ELISPOT assays.
• In vitro and in vivo validation of neoantigen immunogenicity and anti-tumor activity using transgenic mouse models and tumor-bearing mice.

Main Results:

• Multiple high-affinity, mutation-associated neoantigens were identified in all three NSCLC patients.
• Specific neoantigens (ACAD8-T105I, BCAR1-G23V, PLCG1-M425L) demonstrated potent T cell activation and tumor suppression.
• NRTs exhibited significant anti-tumor responses in both in vitro and in vivo models.

Conclusions:

• Immunogenic neoantigens can be effectively screened from NSCLC patients using whole-exome sequencing and machine learning.
• NRTs show efficient anti-tumor responses, validating their therapeutic potential.
• Neoantigen-based personalized immunotherapy is a feasible treatment strategy for NSCLC.