Q1: What is the technology of CAR-T cell Therapy?
A1: Chimeric Antigen Receptor (CAR) T cell Therapy consists in harvesting and engineering T cells -which are responsible to recognize cancer cells- to equip them with a specific receptor that targets the cancer cells. As the name of the therapy describes, a chimera, half cell half artificial receptor, is created and then introduced into the patients’ body to target their own specific cancer cells.
Q2: How to treat with CAR-T?
A2: The first step is to have a target for the CAR-T to identify the attack, i.e. to have a specific antigen. In order to find it, we test using flow cytometry (FCM) or pathological histochemistry in lymphoma/solid tumors whether acute lymphoblastic B or B-cell lymphoma is CD19 positive and can, therefore, become the target. In the case of other cancers, biopsy flow cytometry analysis or immune histochemistry is required.
Q3: Which stage of the disease can be considered for CAR-T cell treatment?
A3: CAR-T cell therapy is indicated for relapsed and refractory leukemia, lymphoma, or solid tumors. For example, cases with no remission after chemotherapy, recurrence after remission, recurrence after bone marrow transplantation, extramedullary leukemia and ineffective routine treatment. In cases in which chemotherapy is difficult to tolerate, such as in advanced age, vital organ damage or personal preference, doctors generally recommend CAR-T treatment.
Q4: What preparations are needed to enroll in the treatment?
1. Patients need to prepare the following medical records: (1) admission records, (2) previous bone penetration examination reports, (3) primary treatments, (4) used chemotherapy regimens, and (5) treatment responses. All documents should be send to our CAR-T Therapeutic Medicine Consultant: by email to firstname.lastname@example.org, or by express courier to GIMI.
2. In case of lymphoma, solid tumors, or extramedullary recurrence in lymphoma before admission to the hospital is also needed: (1) biopsy white films (4-10 sheets), and (2) according to the type of disease, undergo a pathological consultation.
Q5: How to collect peripheral blood lymphocytes to prepare CAR-T?
1. Before collecting the cells, please contact Deng Ying at GIMI. email@example.com.
2. The lymphocytes will be collected when the blood test shows that the white blood cells are more than 3,000. If case of myelosuppression, the physician will evaluate whether the peripheral blood lymphocyte count meets the collection criteria. according to the lymphocyte collecting program
According to the lymphocyte collecting procedure, no granulocyte stimulating factor mobilization is required before the collection.
Q6: How to enroll in treatment?
A6: After the cells have been collected and delivered to the laboratory, patients can be formally enrolled and the treatment can start.
Due to the large number of patients currently needing treatment, we recommend that you complete the cell collection and contact GIMI as soon as possible.
The laboratory will schedule a specific date to infuse CAR-T, and your physician will inform you about the process of pre-infusion of CAR-T and the pretreatment following the fludarabine cyclophosphamide protocol.
Q7: What are the current targets that CAR-T can target?
A7: CART treatment currently has reliable efficacy, the number of successful cases is high. The safest type is CAR-T CD19, which is suitable for B cell leukemia, as well as for B cell lymphoma. Other CAR-T that are currently being developed for use in hematologic malignancies include anti-CD20, CD22, ROR1, CD33, CD8, CD123, CD56, CD38, CD138, and BCMA. For solid tumors, it is present mesothelin, GD2, ROR1, CD56, Her2, EGFRviii, PSMA, CD44v6.
Since new targets are constantly being discovered, your physician will inform you about the most suitable specific CAR to target for you.
Q8: Are there any other options for cancers that do not include CAR-T?
A8: Yes, we have currently two different programs for cancers besides CAR-T cell therapy: Engineered Immune Effector (EIE) and TNT.
The principle of EIE treatment plan is to identify the cancer cell-specific antigen, it is exclusively prepared by GIMI and its function is to destroy cancer cells.
TNT is the abbreviation of Tumor Niche Targeting therapy, a treatment that consists in genetically modified immune cells. In this therapy, specific antibodies, such as PD-1, PD-L1, or CTLA4, are used to target the microenvironment of the tumor.
TNT can be used in combination with CART or EIE, amplifying the effect to eliminate solid tumors.
Q9: Can CAR-T cell treat solid tumors?
A9: Yes. Currently, there are CAR-T cell treatment for neuroblastoma, rhabdomyosarcoma cancer, primitive neuroectodermal tumors (PNET), pancreatic cancer, cholangiocarcinoma, ovarian cancer, breast cancer, small cell lung cancer, endocrine neuronal cancer, muscle tumor and osteosarcoma cancer.
Q10: What kind of cancer patients is CAR-T suitable for?
A10: CAR-T is used for relapsed and refractory acute lymphoblastic leukemia or tumor. It can be used for non-transplant or transplant patients with leukemia and other cancer. In the case of transplantation, the donor's lymphocytes can be used as a source of CAR-T cells.
Q11: What is the cause of death for transplant patients?
A11: Rejection, infection, recurrence are the three major causes of death.
Q12: Can CAR-T replace transplant?
A12: Allogeneic transplantation has a relatively high risk and there is still a possibility of recurrence after transplantation. CAR-T treatment can treat some blood tumors that can only be cured by transplantation. However, because the type of leukemia gene mutation can affect the long-term effects of CAR-T treatment, not all allogeneic transplantation can be treated with CAR-T treatment.
Q13: Can CAR-T be upgraded? Can you only kill the problematic B cells?
A13: Both normal B cells and leukemia/tumor B cells express CD19, but the expression intensity is different. Malignant cells have high expression of CD19. Therefore, although targeting B19 does kill the B cells, it mainly kills malignant cells with high expression intensity. At the same time, after CAR-T infusion, the lack of B cells is temporary, and low immunoglobulins can be compensated by gamma globulin. A new generation of CD19 CAR-T may recognize normal B cells and problematic B cells, but the technology is still under development.
Q14: It is said that B cells in lymphocytes account for 20% and T cells account for 80%. Rituximab targets also B cell. Humans can survive without B cells. Would it be possible not to have any T Cells?
A14: Yes, without T cells, the immune system has great defects and will cause death from infection. Without B cells, lack of antibody immunity can be compensated by infusion of gamma globulin.
Q15: In theory, after CAR-T kills CD19, if it doesn't work, it will disappear by itself. If CD19 is still there, CAR-T will copy itself and continue in the body to fight cancer?
A15: CAR-T cells have similar functions as normal T cells. When there are targeted cells, they will self-expand a lot, but when there is no target cell, they will be in a static state and perform immune monitoring. After successful CAR-T treatment, it can survive for a long time in the body. At present, the new generation of CAR-T of GIMI is equipped with a suicide gene to control the survival of CAR-T.
Q16: Can T cell lymphoma be treated with CAR-T?
A16: There are currently no specific targets to distinguish between normal and abnormal T cells. In the future, target-specific CAR-T will be developed for T-cell lymphoma.
Q17: What are the current targets for B-cell lymphoma?
A17: CD19, CD20, CD22, CD30, ROR1, and other less specific CARs.
Q18: What are the possible side effects after CAR-T treatment?
A18: The main side effect after CAR-T infusion is Cytokine Release Syndrome (CRS). CRS has a tumor killing effect, but it also has a therapeutic risk. It usually occurs from day 4 to the day 9 after the CAR-T infusion, depending on the person it could also happen after 2 weeks. In the initial stages, patients can experience lack of appetite, fatigue and fever; in severe cases can have chest tightness, shortness of breath, hypoxemia, hypotension, rapid heartbeat and even neurological symptoms.
Q19: How to prevent and treat the side effects after CAR-T?
1) Patients with high tumor burden need to reduce tumor burden by effective chemotherapy or radiotherapy, and try to achieve relief or partial remission before CAR-T infusion.
2) Inform rapidly to the doctor and nurse to closely observe body temperature, oxygen saturation and blood pressure.
3) In case fever does not reach 39°, body temperature can be physically cooled. Antipyretic drugs are required for temperature above 39 °. If you have any questions, please contact the doctor as soon as possible.
4) For each of the CAR-T treatment cases, we will provide a CAR-T clinical treatment plan guide in advance. Please contact the doctor for specific questions.
Q20: What is the blood phase change of blood patients after CAR-T reinfusion?
A20: Short-term growth of naive cells may occur in a small number of leukemia patients due to pre-treatment chemotherapy before infusion and post-CAR-T reinfusion, temporary B-cell deficiency and decreased immunoglobulin. The patient may have redness, swelling and heat in the lumps. The doctor will evaluate according to the situation, review the relevant examination in the observation form, and decide on the treatment.
Q21: How is the current treatment of CAR-T?
A21: Currently, in B-cell leukemia, 90% is effective, with a complete response rate of 70%. The total effective rate of lymphoma treatment is close to 70%. We have achieved the same therapeutic effect as CAR-T in the United States.
Q22: How many treatments do you usually need?
A22: It usually takes 1-2 courses. Some patients want to maintain CAR-T for a longer time and may take 4-6 courses.
Q23: What should I do if there is no relief or no reaction after the end of a course of treatment?
A23: The scientific team will investigate further to find the reason and improve treatment accordingly.
Q24: In case of recurrence, can the patient get another treatment of CAR-T?
A24: Yes, CAR-T treatment for both the same and different targets can be performed again after the target is confirmed after the recurrence.
Q25: How often do you need to review after mitigation?
A25: Generally, a review can be conducted on average every one month to two months.
Q26: After transplant, can the patient get CAR-T?
A26: Yes, at this point, the donor's blood can be collected for culture and CAR-T can be prepared.
Q27: After CAR-T, can the patient undergo transplant?
A27: Yes, the two procedures do not interfere with each other.
Q28: After CAR-T, can the patient do chemotherapy?
A28: In principle, chemotherapy/radiotherapy or adrenocortical hormone is contraindicated after CAR-T treatment or during maintenance (sustained remission). Because this will damage the number or function of CAR-T, and even completely remove the CAR-T in the body. Therefore, chemotherapy/radiotherapy can be considered only if it is determined that the progression of the disease cannot be controlled after the CAR-T infusion.
Q29: As a family member, what do we need to pay attention to after returning?
1) Pay attention to whether there is fever, physical discomfort and blood oxygen, abnormal blood pressure.
2) Review regularly, collect a small amount of blood and send it back to the laboratory for testing; usually return to the hospital for follow-up after one month.
3) Nutritional support and immune function support enhance the maintenance of CAR-T in vivo.
Q30: How long after returning can the patient see the effect?
A30: There are individual differences. Generally speaking, after 20 days of leukemia, lymphoma takes about 50-70 days. Imaging studies of bone penetration or tumor burden are not recommended before this time point.
Q31: Can central nervous system leukemia (brain white) be treated with CAR-T?
A31: Yes, like other extramedullary leukemias, brain white can also be treated with CAR-T. In order to achieve the desired therapeutic effect, it is recommended to first control with intramuscular chemotherapy, or brain or brain and spinal cord radiotherapy to reduce tumor burden, in order to limit the chance of recurrence after treatment, and then CAR-T treatment.
Q32: In the case of leukemia, is it feasible to use CAR-T without radiotherapy?
A32: The central nervous system acute lymphoblastic leukemia (CNS-ALL) evolves differently in each stage. In early stages, leukemia can be easily controlled by CAR-T Cell infusion, in later stages, the treatment of the disease is late requires regular radiotherapy or precision radiotherapy.
CAR-T treatment alone is also possible, but there might be complications: if during the treatment of leukemia, there is a relapse or the disease gets worse, radiotherapy will be required. At this moment, the dose of radiotherapy needed might be higher than the dose of usual radiotherapy at the beginning of the disease. Moreover, the T cells infused during the CAR-T cell treatment will be killed during radiotherapy.
Q33: Can severe pulmonary fungal infection be treated with CAR-T?
A33: We have a specific antifungal EIE-CAR-T treatment for patients with this type of leukemia with severe fungal infections. After infusion, tumors and fungi can be treated at the same time, achieving remarkable effects. For these cases, you can consult with GIMI for more information.
Furthermore, there are also EIE-CAR-T treatment specific for anti-CMV or anti-EBV that can be used in leukemia patients with resistance to CMV infection or EBV infection.