Advanced solid tumors: This CAR-T therapy Covering 14 major cancers

Advanced solid tumors: This CAR-T therapy Covering 14 major cancers.  CAR-T therapy has changed the picture of hematological malignant tumor treatment and has become one of the most promising tumor immunotherapies in recent years.

Every year, the global death toll from malignant tumors is as high as 90 million. CAR-T cell therapy is a chimeric antigen receptor T cell immunotherapy. It is currently the most advanced tumor treatment method in the world. It extracts T cells from human blood and transforms them into a tumor that can recognize and eliminate tumors using genetic engineering technology. CAR-T cells are then injected into the patient’s body.

As we all know, CAR-T therapy has changed the picture of hematological malignant tumor treatment and has become one of the most promising tumor immunotherapies in recent years. With four autologous CAR-T therapies targeting CD19
Kymriah and Yescarta, Tecartus, Breyanzi
Successively approved for marketing, the remarkable efficacy of CAR-T therapy has gradually been recognized in the industry, and has become the focus of attention of many cancer friends.

Although CAR-T therapy is limited in the treatment of solid tumors that account for more than 90% of malignant tumors, scholars at home and abroad have made various modifications to CAR-T, and constantly discover new targets for the treatment of various Solid tumors.

The effective rate of anti-cancer is 72%, CAR-T technology breaks the solid tumor barrier

At the 2019 American Association for Cancer Research (AACR) annual meeting, a new type of CAR-T cell technology targeting mesothelin attracted the attention of everyone, and its efficacy data can be described as impressive.

【Research Background】

This clinical trial included 21 patients with relapsed and refractory mesothelin-positive advanced solid tumors who had failed other treatments in the past, including 19 cases of advanced malignant mesothelioma, 1 case of advanced lung cancer, and 1 case of advanced breast cancer. . All patients received LcasM28z combined with PD-1 antibody treatment.

LcasM28z was developed by Adusumilli, deputy director of thoracic surgery at Memorial Sloan Kettering Cancer Center, and his team using the second generation of activated CD28 all-human mesothelin CAR-T cells with Icaspase-9 safety genes.

Moreover, the vast majority of patients have received high-dose chemotherapy for myeloablative pretreatment before CAR-T treatment.
It should be noted that this operation must be carried out in a very experienced top hospital, and a high degree of infection prevention is required.

【Research results】

After 38 weeks of treatment, persistent CAR-T cells can still be detected in the peripheral blood of 13 of 21 patients. 11 patients successfully completed CAR-T injection and at least 3 courses of PD-1 treatment. After at least 3 months of follow-up, 8 of 11 patients had tumor shrinkage, and even 2 patients showed complete disappearance of tumor by PET-CT, and the overall remission rate was as high as 72%.

Next, the editor of Cancer Free Home will review the clinical studies of CAR-T therapy in various cancers one by one, hoping to provide new treatment options for all cancer friends.

Non-small cell lung cancer: PD-1 knockout CAR-T therapy for the first time in lung cancer

ESMO tumor immunity 2018 conference reported the world’s first PD-1 knock-out MUC-1 CAR-T treatment of advanced non-small cell lung cancer preliminary research data, this research is a collaboration between the First Affiliated Hospital of Guangdong Pharmaceutical University and other units Unfolded.

The preliminary results of the study showed that the PD-1 knock-out MUC-1 CAR-T treatment was safe and tolerable. The tumors of some patients were significantly reduced, and the symptoms of all patients in the group were improved.

【Combination immunotherapy 1+1>2】

The antigen selected for this study is MUC-1. The study found that more than 70% of patients with non-small cell lung cancer have abnormal expression of MUC-1, which is an ideal target for CAR-T therapy for non-small cell lung cancer.

【Research result】

The ESMO conference reported the data of 6 patients who were enrolled. In the first 2 weeks after CAR-T cell infusion, the symptoms of all patients were significantly improved, and the tumors were significantly reduced. The size of the tumor in one patient was reduced from 25x19x22mm to 14x10x26mm. In terms of safety, no cytokine release syndrome (CRS) was observed, and no other adverse reactions were recorded in all patients.

EGFR-targeted CAR-T in the treatment of advanced refractory NSCLC

Chinese Professor Han Weidong from 301 Hospital  reported the use of EGFR-targeted CAR-T to treat patients with advanced refractory non-small cell lung cancer with strong EGFR expression (EGFR expression exceeding 50%).

The results of the study showed that the efficacy of 11 patients can be evaluated: 2 patients have significantly reduced tumors, and 5 patients have stable disease.

In Figure A, patient 1 was infused with CAR-T cells. CT scan showed that his pleural effusion was reduced, and the metastatic hilar lymph nodes and pleural nodules were slightly reduced (arrows).

The CT image in Figure B shows that the primary tumor of patient 8 has shrunk (arrow);

The CT examination in Figure C found that patient 9’s pleural effusion absorption and lung lesions significantly subsided after CAR-T treatment.

Liver cancer:

Advanced liver cancer can also be saved! Chinese-only CAR-T clinical trial, reappearing dawn!

The results of a phase I clinical study on the treatment of advanced hepatocellular carcinoma (HCC) with CAR-T cells targeting GPC3 are “coming out”: the safety and effectiveness of the treatment have obtained promising results.

As of July 24, 2019, a total of 13 patients have received CAR-GPC3 T cells. All patients were GPC3-positive, had received surgical treatment, local treatment or systemic treatment, and all carried hepatitis B virus (HBV).

Among them, 2 patients achieved partial remission (PR). The survival rates of all patients at 6 months, 1 year, and 3 years were 50.3%, 42.0%, and 10.5%, respectively. The median survival time (OS) was 278 days (39.7 weeks). ).

Typical cases

The survival time of these two patients was 20.5 months (Figure P13) and 44.2 months (Figure P3), One of the patients with stable disease has survived nearly 4 years!

Ovarian cancer: 

Progression-free survival for 5 months, survival for up to 17 months! The new CAR-T therapy has achieved remarkable results!

On February 18, the world-class academic journal “Journal of Cancer Immunotherapy” published the research results of Chinese medical researchers using CAR-T autocrine PD-1 antibody for the treatment of solid tumors. Clinical data shows that
A patient with advanced refractory ovarian cancer who was treated with this treatment had a progression-free survival of 5 months and a survival rate of 17 months.

This article is also the first international clinical data article using CAR-T autocrine PD-1 antibody for the treatment of solid tumors. The blocking effect of PD-1/PD-L1 inhibitors on PD-1 can significantly enhance the anti-tumor efficacy and reverse immunosuppression of CAR-T cells.

In this study, ovarian cancer patients with a history of chemotherapy failure received two αPD-1-mesoCAR-T cell infusions in combination with apatinib. MRI observed synergistic inhibition of liver metastasis nodules. The patient achieved partial remission and survived for 17 months with mild side effects. The results show,
The combination of CAR-T cells and apatinib will become a new treatment method for advanced/refractory ovarian cancer.

Gastric cancer and pancreatic cancer:

CAR-T challenges solid tumors! The effective rate of treating gastric cancer and pancreatic cancer is 33%

In the field of solid tumors, China has achieved world-renowned achievements and developed the world’s first solid tumor CAR-T therapy targeting Claudin 18.2.

Claudin 18.2 (CLDN 18.2) is a gastric-specific membrane protein, which is considered a potential therapeutic target for gastric cancer and other cancer types. Based on this, Chinese researchers developed the first CAR-T cell targeting Claudin 18.2 in the world.

At the 2019 ASCO annual meeting, the clinical data update of CAR-Claudin 18.2 T cells in the treatment of gastric cancer/pancreatic cancer showed that 12 cases of metastatic adenocarcinoma (7 cases of gastric cancer and 5 cases of pancreatic cancer) were treated by targeting claudin 18.2 CAR T cells. Serious adverse events, treatment-related deaths, or severe neurotoxicity occurred. Among the 11 evaluated subjects: 1 case (gastric adenocarcinoma) had a complete remission; 3 cases (gastric adenocarcinoma, 2 cases of pancreatic adenocarcinoma, 1 case) had partial remission; 5 cases had stable disease; 2 cases had progressed; the overall objective response rate was 33.3%.

In addition, the preclinical research results of CAR-Claudin 18.2 T cells in the treatment of gastric cancer show that CAR-T cells targeting Claudin 18.2 can completely eliminate gastric tumors in a mouse model without off-target toxicity.

Colorectal cancer:
The life span has doubled by 5 times! New CAR-T therapy will carry out human trials

Researchers from the Sidney Kimmel Cancer Center (SKCC) of Jefferson Health stated that CAR-T cell therapy can successfully kill tumors (colorectal cancer) and prevent the metastatic growth of tumors in mouse disease models. Related research results were published in the journal Cancer Immunology Research. It is worth mentioning that the research published in this journal is the last step before entering human clinical trials.

The tumor antigen of this colorectal cancer is called GUCY2C. Director of the Jefferson Department of Pharmacology and Experimental Therapy, Dr. Scott Waldman identified this antigen as a potential biomarker and therapeutic target for colorectal cancer.

In order to more accurately simulate advanced human diseases, in further experiments, Dr. Snook and his colleagues also studied a mouse model of colorectal cancer with lung metastasis, which is a common site of metastasis in colorectal cancer patients.

The results showed that: The mice receiving CAR-T treatment survived within 100 days without metastasis, while the average survival time of the control group was only 20 days, which means that the survival time of the mice receiving CAR-T treatment was 5 times that of the control group. Times!

Breast cancer CAR-T therapy breaks the deadlock, triple-negative breast cancer begins to dawn

At the 2018 San Antonio Breast Cancer Symposium, based on the results of the ongoing Phase I study. CAR-T treatment of advanced triple-negative breast cancer (TNBC) has achieved long-term stable disease. Let’s take a look at the specific research situation.

Jennifer Specht, MD, University of Washington in Seattle, provided data on seven ROR1-expressing triple-negative breast cancer (TNBC) patients who are receiving CAR-T cell therapy at five dose levels.

All patients receiving treatment (age range 27-67 years) have at least 3 lines of previous transfer treatment experience. 3 patients received up to 9 front-line treatments (1 line represents one plan, and the treatment failed to change to another plan, namely 2 lines, 3 lines…), and 1 patient received 11 front-line treatments.

The final results are also surprising：

After CAR-T treatment, the patient’s condition lasted longer, one for 15 weeks and the other for 19 weeks. No follow-up treatment plan had a more therapeutic effect than CAR-T cells.

In addition, one patient was in stable condition after the first reinfusion of CAR-T, and the partial response lasted for 14 weeks after the second reinfusion (for advanced triple-negative breast cancer, it is not easy to extend the survival period by one week!).
(If you want to know more about CAR-T frontier clinical research information at home and abroad, please continue to pay attention to the website of Cancer Free Home)

In recent years, scientists have made considerable efforts to develop new approaches to barriers to solid tumors and adopt optimized strategies for CAR-T therapy for these specific indications. We look forward to the fact that more and more preclinical/clinical trial data can piece together a complete puzzle, fully demonstrating the true strength of CAR-T cell therapy in the treatment of advanced solid tumors.

(source:internet, reference only)

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