Related Experiment Video
Updated: May 4, 2026
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
Update on immune checkpoint inhibitors in lung cancer
1Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Ben.Creelan@Moffitt.org.
Background:
The immune checkpoint proteins, including the B7/CD28 receptor superfamily, have become increasingly important targets for pharmacologic blockade. Several classes of new agents have impressive clinical activity, and their eventual approval for treatment of lung cancer seems likely.
Methods:
This article discusses the current development of these agents, including the CTLA-4, PD-1, and PD-L1 inhibitory pathways, killer immunoglobulin receptor (KIR ) inhibition, and other checkpoint proteins.
Results:
Ipilimumab in combination with chemotherapy has exhibited encouraging results in small-cell and non-small-cell lung cancer alike. Reported phase I trials of the monoclonal antibodies nivolumab, MK-3475, MEDI4736, and MPDL3280A are demonstrating durable overall radiological response rates in the 20% to 25% range in lung cancer. This exceptional activity includes squamous lung cancers, a population historically bereft of significant therapeutic advances. Retrospective examination of tumor PD-L1 expression suggests that PD-L1 may eventually be evaluable as a predictive biomarker. Dual checkpoint blockade strategies, such as those combining anti-CTLA-4, anti-LAG-3, or anti-KIR, are being tested to increase the proportion and durability of tumor responses. Examination of acquired immune resistance and post-immunotherapy relapse strategies are underway.
Conclusions:
These emerging antibodies hold great potential for the systemic control of epithelial cancers such as lung cancer.
Insights
New immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 pathways show promise for lung cancer treatment. These agents, including novel monoclonal antibodies, demonstrate durable responses, especially in historically difficult-to-treat squamous lung cancers.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Immune checkpoint proteins, part of the B7/CD28 superfamily, are crucial targets for cancer therapy.
- Pharmacologic blockade of these checkpoints has shown significant clinical activity in lung cancer.
Purpose of the Study:
- To review the development of immune checkpoint inhibitors for lung cancer treatment.
- To discuss agents targeting CTLA-4, PD-1, PD-L1, and KIR pathways.
Main Methods:
- Review of current clinical development of immune checkpoint inhibitors.
- Discussion of specific agents like ipilimumab, nivolumab, MK-3475, MEDI4736, and MPDL3280A.
- Exploration of dual checkpoint blockade strategies and resistance mechanisms.
Main Results:
- Ipilimumab combined with chemotherapy shows positive results in both small-cell and non-small-cell lung cancer.
- Phase I trials of monoclonal antibodies report durable radiological response rates of 20-25% in lung cancer patients.
- Significant activity observed in squamous lung cancers, with PD-L1 expression as a potential predictive biomarker.
Conclusions:
- Emerging immune checkpoint antibodies offer significant potential for systemic control of epithelial cancers like lung cancer.
- Further research into dual blockade and resistance mechanisms is ongoing to enhance therapeutic outcomes.
Related Concept Videos
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
02:56Treatment Resistant Cancers