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Article source: Medical Rubik's Cube Pro
Author: Haimer
Immune checkpoint inhibitors represented by the PD-1/L1 antibody have revolutionized the treatment of a variety of cancers in the past few years.
With Kangfang Bio/Zhengda Tianqing’s PD-1 antibody Anike® (generic chemical name: Pianprizumab injection) has been approved for marketing, and 13 PD-1/L1 antibodies have participated in commercial competition worldwide
.
How can "players" break through such a crowded PD-1/L1 antibody track? In addition to expanding new indications, the development of combination therapy is also a general direction
.
Combination therapy can effectively improve the limitations of PD-1/L1 antibody monotherapy with low effective rate (20%-30%)
Researchers at the Moffitt Cancer Center in the United States initiated an evaluation of the PD-1 antibody nivolumab (trade name: Odivo) in combination with tumor infiltrating lymphocytes (TIL) for the treatment of advanced non-small cell lung cancer (NSCLS) Phase I clinical trial
.
On August 12, the top medical journal Nature Medicine reported the results of the trial
TIL is equivalent to CAR-T and TCR-T as adoptive cell therapy
.
Previously, TIL therapy has shown surprising anti-cancer effects in melanoma, breast cancer, cervical cancer, cholangiocarcinoma, and colorectal cancer
This single-arm, open-label phase I clinical trial (NCT03215810) included a total of 20 patients with advanced NSCLC
.
The primary endpoint of the study is safety, and secondary endpoints include objective response rate, duration of response, and T cell persistence
Simply put, in this study, scientists first isolated and screened TIL cells from patient tumors, and then added the cytokine IL-2 to activate them to maximize the expansion of immune cells
.
Finally, after determining the activity and effectiveness of the cells, the TIL cells are re-infused into the patient
The production process of TIL cells (Source: Nature Medicine)
Before TIL treatment, every patient received nivolumab treatment
.
If the patient develops disease progression after receiving PD-1 antibody treatment, he will receive a personalized TIL infusion and then receive nivolumab maintenance treatment
Source: Nature Medicine
According to the pre-set standard for the occurrence of serious toxic events of ≤17%, the study reached the safety endpoint
.
In terms of efficacy, of the 13 evaluable patients, 3 cases were confirmed to have remission, and 11 cases had reduced tumor burden, with a median optimal change value of 35%.
In exploratory analysis, the researchers found that after TIL treatment, they detected T cells that could recognize multiple cancer mutations, and these T cells were enriched in patients who responded to treatment; in addition, neoantigens in peripheral blood after treatment The clonotype of sex T cells increased and persisted
.
Based on these results, scientists believe that autologous TIL therapy has both safety and clinical activity, and it may be used in combination with PD-1 antibody as a new treatment for metastatic NSCLC
.
At the same time, Stanley R.
Riddell of the Fred Hutchinson Cancer Research Center at the University of Washington also published an article on Nature Medicine to comment on this result
.
Stanley expressed excitement about the anti-tumor activity of TIL therapy in PD-1 resistant patients, and also raised some questions
.
TIL therapy requires tumor resection and biopsy, which is a higher risk for some NSCLC patients
Reference materials:
[1] Benjamin C.
Creelan et al.
Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.
NatureMedicine.
(2021).
[2] Joshua R.
Veatch et al.
Tumor-infiltrating lymphocytes make inroadsin non–small-cell lung cancer.
Nature Medicine.
(2021).
