How researchers are using cell and gene therapy for lung cancer

Jun 01, 2022
Devin Golden

How researchers are using cell and gene therapy for lung cancer

An illustration of lung cancer

According to the LUNGevity Foundation, more than 230,000 people in the United States are diagnosed with lung cancer each year. This number equates to approximately one person every two minutes.

Advances in immunotherapy have thankfully helped alleviate the patient burden. This progress is providing more treatment options beyond chemotherapy and radiation.

The latest U.S. Food and Drug Administration approval is the immunotherapy drug Opdivo® (generic name “nivolumab”) for use in non-small cell lung cancer (NSCLC) and other solid tumors. Opdivo can be used with chemotherapy before surgery in cases of early-stage NSCLC.

This approval is one of several immunotherapy or targeted therapy drugs for lung cancer. Immune checkpoint inhibitors like Opdivo have some limitations, however, so researchers are also pursuing cell and gene therapies like CAR T-cell therapy for this cancer.

Alliance for Cancer Gene Therapy (ACGT) supports the potential of cell and gene therapy as a lung cancer treatment. Here is a summary of some recent developments in using cell and gene therapy to treat lung cancer.

Alliance Research Fellow focusing on tumor macrophages

ACGT is currently funding the work of Brian Brown, PhD, a researcher at Icahn School of Medicine at Mount Sinai Hospital. Dr. Brown has received a grant for his research into creating chimeric antigen receptors (CARs) that kill tumor macrophages – hopefully removing a major barrier to successful immunotherapy.

Macrophages are a type of cell that protects us from infections. However, tumor cells can reprogram macrophages to defend the cancer against T cells. This alteration of macrophages can render immunotherapy treatments for lung cancer ineffective. The macrophages essentially become a patient’s opponent instead of an ally.

Dr. Brown’s intent is to develop CARs that target macrophages in tumor cells while sparing those in healthy tissue. He provided an update on his research during the annual ACGT Scientific Advisory Council annual meeting in January. In preclinical testing of the programmed antigen receptors, Dr. Brown reported his treatment caused a significant reduction in lung tumor size in mice, as shown on imaging scans.

ACGT continues to look for innovative projects like Dr. Brown’s work. Our intent is to fund breakthrough research that can translate to clinical trials and eventually become widely accessible to cancer patients.

With your donation, Alliance for Cancer Gene Therapy can increase its financial support of each research program and possibly fund a higher number of programs. Please consider donating today to join our alliance and help us improve the future of cancer treatment.

Adding a tumor-suppressing gene to fight lung cancer

One type of cancer gene therapy adds genes that cause cancer cells to die. This form of gene therapy is intended to stop cell replication and promote cancer cell death.

REQORSA™ is a potential immunogene therapy being studied in multiple trials for non-small-cell lung cancer. Manufactured by Genprex, the therapy’s active ingredient is TUSC2, a tumor-suppressing gene encapsulated in a nanoparticle. REQORSA is injected intravenously, making it the first systemically delivered gene therapy to reach human clinical trials.

After infiltrating the cancer cell, TUSC2 interrupts cell signaling pathways to prohibit cell replication. The gene also re-establishes pathways for signaling programmed cell death, or apoptosis.

REQORSA is being studied in four new clinical trials for non-small-cell lung cancer both as a monotherapy and in combination with targeted therapies. The first patient in the Acclaim-1 clinical trial was recently dosed, and enrollment opened in another trial pairing the therapy with immune checkpoint inhibitor drug Keytruda, signaling progress in discovering whether this gene therapy can work for lung cancer.

Gene deletion with safety-switch CAR T cells

One of the main issues with cell and gene therapy for solid tumors – like lung cancer – is developing therapies that do not damage healthy cells. This issue occurs because many cancer cells and healthy cells share the same protein biomarkers.

A2 Biotherapeutics’ Tmod™ CAR T-cell therapy addresses this roadblock. The novel therapy utilizes two receptors added in laboratories to help Tmod CAR T cells differentiate between cancer cells and healthy tissue.

They focus on genetic deletions that occur when healthy tissue turns cancerous. One receptor, called an activator, is programmed to look for a specific antigen expressed on cancer cells. The other receptor, a blocker, seeks the antigen created by whatever gene the cancer cells lost.

If the Tmod CAR T cells’ activator receptor links with another cell but the blocker receptor doesn’t, then the T cell registers the other cell as cancerous. If both the activator and blocker receptors are engaged, the Tmod programming labels the cell as healthy.

Two scientific papers published preclinical findings related to the Tmod T cells. The first, in Science Translational Medicine, described Tmod cells moving toward a phase 1 clinical trial for colon cancer.

In the Journal for ImmunoTherapy of Cancer, Tmod T cells were reported as a potential lung cancer treatment. The antigen target for this cancer is mesothelin, while HLA (a group of human leukocyte agents) is the safety switch signaling to the T cells that they’ve found a harmless cell.

In summary, while some types of immunotherapy have made advances in treating lung cancer, there is also progress in developing cell and gene therapies as impactful treatment options.

Page sources

  1. Lung Cancer Statistics. LUNGevity Foundation. Retrieved from: https://www.lungevity.org/for-supporters-advocates/lung-cancer-awareness/lung-cancer-statistics. Accessed: 03/08/2022.
  2. FDA approves neoadjuvant nivolumab and platinum-doublet chemotherapy for early-stage non-small cell lung cancer. U.S. Food and Drug Administration. Retrieved from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-nivolumab-and-platinum-doublet-chemotherapy-early-stage-non-small-cell-lung. Accessed: 03/08/2022.
  3. The First Systemically Delivered Gene Therapy Used for Cancer in Humans. Genprex. Retrieved from: https://www.genprex.com/technology/reqorsa/. Accessed: 03/04/2022.
  4. Genprex Announces First Patient Dosed in Phase 1/2 Acclaim-1 Clinical Trial of REQORSA™ Immunogene Therapy in Combination with Tagrisso® to Treat Non-Small Cell Lung Cancer. Biospace. Retrieved from: https://www.biospace.com/article/releases/genprex-announces-first-patient-dosed-in-phase-1-2-acclaim-1-clinical-trial-of-reqorsa-immunogene-therapy-in-combination-with-tagrisso-to-treat-non-small-cell-lung-cancer/. Accessed: 03/04/2022.
  5. Our Science. A2 Bio. Retrieved from: https://www.a2bio.com/science/. Accessed: 03/04/2022.
  6. A2 Bio Publishes Key Preclinical Findings Demonstrating Potential of Its Highly Selective Tmod™ Cell Therapy Platform to Revolutionize the Treatment of Solid Tumors in Select Patients. Business Wire. Retrieved from: https://www.businesswire.com/news/home/20220302005008/en/A2-Bio-Publishes-Key-Preclinical-Findings-Demonstrating-Potential-of-Its-Highly-Selective-Tmod%E2%84%A2-Cell-Therapy-Platform-to-Revolutionize-the-Treatment-of-Solid-Tumors-in-Select-Patients. Accessed: 03/04/2022.