Adoptive Cell Therapy

Adoptive cell therapy uses a patient’s own immune cells or genetically engineered immune cells that are altered to recognize the patient’s tumor cells.2 There are several different types of adoptive cell therapy being evaluated for solid tumors, including lung cancer.

In one approach, the tumor infiltrating lymphocytes (TILs), which are immune cells in and around the patient’s tumor, are removed and activated outside the patient’s body. The patient undergoes lymphodepletion with chemotherapy, and then the now-activated TILs are infused back into the patient. The newly activated TILs are hypothesized to recognize and target tumor cells.

Another approach is the use of CAR-T therapies, which are already in use for some hematologic cancers.2 To produce CAR T cells, the patient’s T cells are collected and are modified to express components of antibodies that attach to a TCR, which promotes T-cell activation while also enabling the now activated T cells to target specific antigens. Patients undergo lymphodepletion with chemotherapy and then the CAR T cells are infused into the patient. Although this approach is being explored in solid tumors, there have been major challenges that have limited their development in this setting. A major challenge has been finding an antigen that the CAR T cells can target without causing substantial toxicity.


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An approach that is also in the early stages of development is T-cell receptor (TCR) immunotherapy.2 T cells are collected from the patient and their TCRs are altered to recognize the specific antigens. Clinical trials are now focusing on using specific tumor antigens to limit toxicities. The altered T cells are then infused back into the patient, where they target and kill tumor cells.

Personalized Cancer Vaccines

The purpose of cancer vaccines is to sensitize the patient’s immune system to their tumor cells.2 The vaccines either enhance the patient’s existing immune response or generates a new response. Similar to some of the adoptive cell therapy approaches, a major challenge is finding an optimal and specific tumor cell antigen to target. There are ongoing clinical trials evaluating personalized cancer vaccines used alone or in combination with immune checkpoint inhibitors in NSCLC.

Conclusion

Immuno-oncology is a burgeoning field, with immune checkpoint inhibitors already approved for use in advanced lung cancer and additional approaches in clinical trials.

References

  1. US Food and Drug Administration. Hematology/oncology (cancer) approvals & safety notifications. Website. Updated July 8, 2020. Accessed July 2, 2020.
  2. Solomon BJ, Beavis PA, Darcy PK. Promising Immuno-Oncology Options for the Future: Cellular Therapies and Personalized Cancer Vaccines. Am Soc Clin Oncol Educ Book. 2020;40:e253-e258.
  3. ClinicalTrials.gov. Nivolumab and Tumor Infiltrating Lymphocytes (TIL) in Advanced Non-Small Cell Lung Cancer. NCT03215810. https://clinicaltrials.gov/ct2/show/NCT03215810. Accessed July 2, 2020.
  4. ClinicalTrials.gov. Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin. NCT02414269. https://clinicaltrials.gov/ct2/show/NCT02414269. Accessed July 2, 2020.
  5. ClinicalTrials.gov. TCR-engineered T Cells in Solid Tumors With Emphasis on NSCLC and HNSCC (ACTengine) (ACTengine). NCT03247309. https://clinicaltrials.gov/ct2/show/NCT03247309. Accessed July 2, 2020.
  6. ClinicalTrials.gov. Study of the Immune Response of MUC1 (Mucin1) Peptide Vaccine for Non-small Cell Lung Cancer. NCT01720836. https://clinicaltrials.gov/ct2/show/NCT01720836. Accessed July 2, 2020.