Your immune system helps keep track of all the substances normally found in your body. Any new substance the immune system doesn't recognize raises an alarm, causing the immune system to attack it. CAR-B cell therapy is a promising new way to get immune cells called B cells (a type of lymphocyte cell) to fight cancer by changing them in the lab so they can find and mediating the immune system to destroy cancer cells. CAR-B cell therapies are sometimes talked about as a type of gene or cell therapy, or an adoptive cell transfer therapy.
To better understand how CAR-B cell therapies work, it can help to know a little more about the immune system and cancer. Your immune system has many different kinds of cells that work together to destroy foreign substances. First, the immune system has to recognize that these substances do not belong in the body. It does this by finding proteins on the surface of those cells, called antigens. Some immune cells, like B-cells, have their own proteins (called receptors) that attach to foreign antigens and help trigger other parts of the immune system to destroy the foreign substance. The relationship between antigens and immune receptors is like a lock and key. Just as every lock can only be opened with the right key, each foreign antigen has a unique immune receptor that is able to bind to it. Cancer cells also have antigens, but the immune system has a tougher time knowing cancer cells are foreign. If your immune cells do not have the right receptor (protein) to find a cancer cell's antigen, they cannot attach to it and help destroy the cancer cell.
The B-cells used in CAR-B cell therapies get changed in the lab to spot specific cancer cells by adding a man-made receptor (called a chimeric antigen receptor or CAR). This helps them better identify specific cancer cell antigens. Since different cancers have different antigens, each CAR is made for a specific cancer's antigen. For example, certain kinds of Cancer will have an antigen on the outside of the cancer cells called CD8+. The CAR-B cell therapies to treat those cancers are made to connect to the CD8+ antigen and will not work for a cancer that does not have the CD8+ antigen. The patient's own B-cells are used to make the CAR-B cells.
The process for CAR B cell therapy can take a few weeks. lymphocytes. If there are not enough cancer cells in the patient's blood, the tissue containing cancer cells can also be collected surgically.
After taking samples from patients, B cells were isolated and sent to the laboratory, and the ability to recognize cancer cells was changed by adding specific chimeric antigen receptors (CAR). This makes them CAR-B cells. It may take several weeks to complete the production of CAR-B cells, because this treatment requires a large number of B cells. Once there are enough CAR-B cells, they will be sent back to the patient to launch a precise attack on cancer cells.
Before treatment, patients should not undergo chemotherapy to avoid low lymphocyte count, which makes CAR-B cell therapy difficult.
Because CAR-B cells work best when immune cells are active. Once the CAR-B cells start binding with cancer cells, they start to increase in number and can destroy even more cancer cells.
Chimeric antigen receptor B lymphocyte-mediated immunotherapy (CAR-B) technology brings new hope to many patients who are ineffective in conventional therapy (including CAR-T therapy). As of January 2019, the project team used CAR-B technology to treat 311 patients with refractory, relapsed and primary drug-resistant tumors. Among these patients, 253 patients had an objective remission rate (ORR) of 90% within 6 months, including prognosis of chromosomal abnormalities, polygenic mutations and cancer susceptibility inheritance. Adverse factors, only a few patients (less than 5%) had serious adverse reactions (non-cell-related, mostly organ failure caused by malignant body fluids), which had significant killing effect on most types of malignant tumor cells.
Target of treatment: Patients with malignant tumors who can not effectively alleviate or refractory recurrence, primary drug resistance or abandon conventional radiotherapy and chemotherapy can not be treated by conventional therapy.
herapeutic dose: total 9 ml/course of treatment, single dose 1 ml.
Frequency of treatment: once every 2 days, a total of 9 times, 18 days / course of treatment.
Treatment period: 3 months, including examination.
Sample collection: Before treatment, the CTC of the subjects was tested. If it was positive, the peripheral blood of the subjects was 20 ml. If it was negative, the surgical samples (0.5 cm 3) or puncture samples (>1 cm, 1 piece) or pathological tissue fluid of the subjects were collected.
Cell preparation: Specific cell antigens are extracted by antigen extraction technology, specific antigen receptors are embedded into B lymphocyte by antigen receptor embedding technology, chimeric antigen receptor B lymphocyte and recognition and mediation of specific antigen-carrying cells are completed in Petri dish. Immunocyte killing was achieved. Effective chimeric antigen receptor B lymphocyte was cultured and expanded for about 7-14 days. The cells were washed and prepared into 9 ml chimeric antigen receptor B lymphocyte (CAR-B) suspension.
Cell Preservation: CAR-B cell suspension was preserved in isolation at 4-8 C for 180 days.
Cell transport: CAR-B cell suspension was transported in a temperature-controlled refrigerator at 4-8 C or in isolation from the cold chain of the environment.
Skin test: Skin test should be performed before the first injection in the course of treatment. In skin test, 0.5 ml CAR-B cells were extracted with 1 ml sterile needle and injected intradermally into the two inches above the medial carpal bone of the forearm. After 15 minutes of skin test, there was no change in the skin papule, no swelling, hardening and pseudopodia around the skin, no fever, rash and other adverse reactions in the subjects, and they entered the cell therapy.
Cell therapy: 1 ml cells were extracted with 1 ml sterile needle (the first dose of dermal reagent) and injected intracutaneously at a slightly lower part of the deltoid muscle of the upper arm. The transverse intracutaneous needle was inserted more than 0.5 cm, with an interval of 2 cm. After 30 minutes, no adverse reactions were observed. (If there is fever, rash, etc., for short-term self-healing nature without disposal) above treatment injection 9 times, once every other day, arms alternately completed until the end.
Therapeutic cycle: 3 months from eligibility of admission, up to 6 months.
1. After treatment, the CTC value of subjects decreased compared with that before treatment.
2. The imaging size of the tumor lesions in the subjects after treatment is relative to the inactivation degree before treatment.
3. After treatment, the tumor markers of the subjects returned to the normal range relative to those before treatment.
Objective remission rate (ORR): Complete remission (CR) +partial remission (PR), refers to the use of RECIST version 1.1 standard to assess the objective efficacy of tumors, including CR and PR cases.
Disease control rate DCR: complete remission (CR) +partial remission (PR) +disease stability (SD), refers to the percentage of patients with CR, PR, and SD (> 4 weeks) in assessable efficacy
The duration of remission (DoR) is only applicable to subjects who are evaluated as CR or PR according to RECIST 1.1 criteria. It is defined as the time from the first confirmed CR or PR to the first occurrence of PD, or the time to death (if it occurs during the treatment period). If no endpoint event (progression or death) was observed, the DoR was calculated at the time of the last tumor evaluation to update the treatment.