In B-cell malignant hematological tumors, since the targets for tumor cells such as CD19 are also expressed on the surface of normal B cells, CAR-T cells will kill normal B cells while clearing tumor cells. Moreover, CAR-T cells can persist in the body for a long time and exert effects, so normal B cells can be deficient in the body for a long time, resulting in B-cell depletion, which in turn leads to decreased immunoglobulin levels and susceptibility to various infections, especially viral pneumonia, which can progress to respiratory failure and endanger life in a short period of time. Therefore, patients after CAR-T cell therapy can regularly supplement immunoglobulin, which is especially important for pediatric patients and patients who have received allogeneic hematopoietic stem cell transplantation before CAR-T cell therapy. Adult patients who have not received hematopoietic stem cell transplantation may have their immune function compensated through other mechanisms. Closely observe infection symptoms, and immunoglobulin supplementation can be appropriately given in the early stage, but long-term immunoglobulin supplementation may not be necessary later.
Lymphoma patients themselves suffer from immune deficiency diseases. In addition, CAR-T therapy is an immune therapy that sacrifices B cells in exchange for health. Therefore, after CAR-T, B cells are suppressed for a considerable period of time, and immunoglobulin needs to be supplemented through infusion to compensate for the deficiency and improve immune capacity. Transplant patients need long-term immunoglobulin infusion, while general CAR-T patients need immunoglobulin infusion in the early stage, and later the body will produce the required immunoglobulin through other compensatory mechanisms.
Therefore, apart from being a susceptible population for infection, CAR-T patients have no other abnormalities.
In CAR-T therapy, tumor cells need to have different targets, such as: CD19, 20, 22, 30, BCMA, 79B, etc. People with good efficacy have constant targets with strong expression and good therapeutic effects.
After treatment, a certain proportion of patients' tumor cells will lose targets, resulting in relapse even when CAR-T function is still very strong. At this time, CAR-T cannot attack tumor cells because there is no target.
Target loss is divided into two situations: complete loss and low expression.
We had an elderly patient who, after receiving CAR-T therapy, completely lost the original target and transformed into another type of cell. Thus, even though his B cells were still 0, the tumor cells were no longer controlled by CAR-T. The reason for this situation was that the previous treatments were too many, and repeated treatments had cultivated many tumor branches to escape attack.
In this situation, we can reselect targets, use fully human sources, use low-density recognition technology, and combine with autologous transplantation to enable some patients to achieve remission again.
Therefore, off-target is generally not a problem with CAR-T, but a problem with tumor cells.
CAR-T therapy has limited efficacy in solid tumors, which account for more than 90% of malignant tumors. However, it is widely used in hematological diseases, including lymphoma, leukemia, multiple myeloma, and other hematological malignancies. It has also been successfully extended to autoimmune diseases such as systemic lupus erythematosus and immune thrombocytopenia. In terms of solid tumors, extensive research has been conducted in many areas including liver cancer, breast cancer, ovarian cancer, gastric cancer, and pancreatic cancer, but the efficacy in solid tumors remains to be observed.
Currently, CAR-T therapy has made significant progress in the treatment of hematological malignancies, showing good therapeutic effects on some blood tumors such as leukemia, lymphoma, and multiple myeloma. The most famous example is Emily, an American leukemia patient who was diagnosed with B-cell acute lymphoblastic leukemia at the age of 5. She received CAR-T cell immunotherapy in 2010, and this year marks her 15th year of cancer-free survival. At the same time, the approval of 5 CAR-T products also confirms the reliable efficacy of this therapy in hematological tumor treatment. However, it is not the "complete cure for cancer" as widely rumored online. CAR-T therapy is still continuously evolving, committed to improving patient prognosis and quality of life.
