Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Dec 7:16:17588359241302021.
doi: 10.1177/17588359241302021. eCollection 2024.

Next-generation immunotherapy: igniting new hope for lung cancer

Molly S C Li  1 , Andrew L S Chan  1 , Kevin K S Mok  2 , Landon L Chan  1 , Tony S K Mok  1
Affiliations
Review

Next-generation immunotherapy: igniting new hope for lung cancer

Molly S C Li et al. Ther Adv Med Oncol. .

Abstract

Adoption of immunotherapy has completely transformed the treatment landscape of cancer. Patients with advanced cancer treated with immunotherapy may benefit from durable tumor response and long-term survival. The most widely used immunotherapy in solid tumors is anti-programmed-death (ligand) protein (PD-(L)1), which is now an integral part of non-small cell lung cancer (NSCLC) treatment irrespective of histological cell types and tumor stage. However, the vast majority of patients with advanced NSCLC treated with anti-PD-(L)1 still develop therapeutic resistance, and the prognosis after anti-PD-(L)1 resistance is poor. Resistance mechanisms to PD-1 blockade are often complex and encompass a combination of defects within the cancer-immunity cycle. These defects include failure in antigen presentation and T-cell priming, presence of co-inhibitory immune checkpoints, inability of immune cells to infiltrate the tumor, and presence of immunosuppressive tumor microenvironment. Recently, advances in drug design, genomic sequencing, and gene editing technologies have led to development of next-generation immunotherapies that may potentially overcome these resistance mechanisms. In this review, we will discuss the anti-PD-(L)1 resistance mechanism landscape in NSCLC and four novel modalities of immunotherapy in detail, namely novel immune checkpoint inhibitor and targeted therapy combinations, bispecific antibodies, cancer vaccine, and cell therapy. These novel therapeutics have all demonstrated early clinical data in NSCLC treatment and may work synergistically with each other to restore anticancer immunity. In addition, we share our perspectives on the future promises and challenges in the transformation of these novel immunotherapies to standard clinical care.

Keywords: adoptive cell therapy < immunotherapy; bispecific antibodies; cancer vaccines < immunotherapy; checkpoint inhibitors < immunotherapy; lung cancer.

Plain language summary

Next generation immunotherapy in lung cancer Immune checkpoint inhibitor with anti-programme-death (ligand) protein (PD-[L]1) is the standard of care for lung cancer treatment however therapeutic resistance is common. Various mechanisms are implicated in immune checkpoint inhibitor resistance. Recently, new generations of immunotherapies including novel immune checkpoint inhibitors, bispecific antibodies, cancer vaccine and cell therapy, have been developed. These novel therapeutics have demonstrated early promising data in lung cancer treatment. In this review, we will discuss these novel immunotherapies in detail and share our perspectives on the future promises and challenges in moving them to standard clinical care.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Novel immunotherapy approaches with emerging data in lung cancer. Created with Biorender.
See this image and copyright information in PMC

References

    1. Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest 2007; 117(5): 1137–1146. - PMC - PubMed
    1. Nishimura H, Nose M, Hiai H, et al.. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11(2): 141–151. - PubMed
    1. Dong H, Strome SE, Salomao DR, et al.. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8(8): 793–800. - PubMed
    1. Budimir N, Thomas GD, Dolina JS, et al.. Reversing T-cell exhaustion in cancer: lessons learned from PD-1/PD-L1 immune checkpoint blockade. Cancer Immunol Res 2022; 10(2): 146–153. - PubMed
    1. Brahmer JR, Tykodi SS, Chow LQ, et al.. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366(26): 2455–2465. - PMC - PubMed

LinkOut - more resources