1.What is biological therapy?
Unlike traditional chemical drugs, biological therapy refers to the use of new biotechnology to prepare cells, biological macromolecules (nucleic acids, proteins and peptides) or small molecules that regulate biological reactions as special “drugs”, which is one of the key development directions in the field of biomedicine in the 21st century.
2.What are the biological treatments for tumors?
(1) Cytokines, such as interferon and interleukin, etc.
(2) monoclonal antibodies.
(3) immune effector cells, such as dendritic cells (DC) and cytokine-induced killer cells (CIK), etc.
(4) Biological vaccines.
(5) genetic drugs.
(6) Non-cytotoxic small molecule drugs that act on specific molecular targets.
3.What is the purpose of immunotherapy for tumor patients?
To stimulate the reactivity of T lymphocytes to tumor-related antigens by specific means, so as to kill or inhibit tumor growth.
4.What are the ways to activate anti-tumor T cells?
(1) Stimulation of tumor-associated antigen-activated immune presenting cells.
(2) Direct activation by stimulation of multiple cytokines in vitro.
(3) Other non-specific pathways such as immune enhancers.
5.What is DC cell?
Dendritic cells are specialized antigen-presenting cells that can efficiently take up, process and handle antigens, and can present the processed antigen information to T cells, etc., enhancing the specificity of T cells for antigen recognition. The discoverer, Dr. Ralph Steniman, was awarded the 2011 Nobel Prize in Physiology and Medicine.
6.What is a DC cell vaccine?
DC vaccine refers to the co-culture of immature DC cells of patient’s own origin with tumor antigens in vitro, to induce DC maturation through a series of biotechnological means while promoting and enhancing their ability to present specific tumor antigens, and when the DC cells thus treated are injected into the body, they will stimulate the body’s own ability to generate specific anti-tumor immune responses. In most cases, DC vaccines are prepared using patients’ own tumor specimens and are personalized treatments. In 2010, the US FDA officially approved a non-personalized DC vaccine (Sipuleucel-L) for the treatment of prostate cancer for clinical use.
7.How does DC cell vaccine exert anti-tumor effect?
DC vaccine has tumor specific antigen presentation ability, and when injected into the body, it will present the tumor specific antigen information to immune cells such as T cells, and the immune cells receiving the tumor antigen information can effectively identify the immune escape tumor cells and generate anti-tumor response through various ways such as secretion of cytokines, so as to inhibit tumor growth and remove residual tumor cells in the body, and prevent tumor recurrence through It can also prevent tumor recurrence through memory effect.
8.What patients are suitable for DC vaccine therapy?
In theory, patients with tumor tissue specimens can be treated with DC vaccine, and there are indications for a variety of solid tumors and hematologic tumors. In recent years, DC vaccine has made great progress in the treatment of lymphoma, prostate cancer, colorectal cancer, melanoma, multiple myeloma, breast cancer, ovarian cancer, brain glioma and kidney cancer.
9.What are CIK cells?
A cytokine-activated killer (CIK) cell with high proliferative capacity and high cytotoxicity was first reported by Stanford University School of Medicine in 1991, combining the non-MHC-restricted killing activity of NK cells with T-cell receptor-mediated specific killing activity. In response to the demand for clinical tumor therapy, the technology for preparing these cells has been developed and improved, and can now be prepared efficiently to the order of therapeutic demand.
10.How do CIK cells exert their anti-tumor effects?
(1) Recognition of tumor cells by surface adhesion molecules.
(2) Release perforin-granzyme to lyse tumor cells.
(3) Secrete various cytokines (such as IFN-g, TNF-a, IL-2, etc.) to directly inhibit tumor growth.
(4) Inducing apoptosis of tumor cells through the Fas pathway.
(5) Indirectly kill tumor cells by regulating the body’s immune system.
11.Which patients are suitable for CIK cell therapy?
Theoretically, all tumors other than T/NK cell lesions are suitable for CIK cell therapy. From the clear reports, the application of CIK cells in the following tumors can effectively prolong the survival: many hematological malignant diseases, many digestive system tumors, non-small cell lung cancer, hepatocellular carcinoma, some ovarian cancer, breast cancer, etc.
12.What patients are suitable for DC combined with CIK cell therapy?
Theoretically, all patients who have indications for CIK cell therapy and have access to tumor antigens (specimens) can undergo DC combined with CIK cell therapy. In essence, there is no conflict between the combined application of the two.
13.When is it appropriate to use immune cell therapy?
Theoretically, immune cell therapy can be started at any time, but when the tumor load (the number of tumor cells in the body) in the patient’s body is reduced to a certain level, immune cell therapy may achieve better tumor clearing effect.
14.How to determine the course of immune cell therapy?
At present, there is no consistent course of immune cell therapy internationally. However, from the clinical observation results, they all follow a common rule, that is, the more times of infusion, the better the efficacy. Take CIK cells as an example, generally after 4 courses of infusion, the efficacy will be evaluated before deciding whether to continue to complete the subsequent courses.
15.How does immune cell therapy alternate with conventional therapy?
Generally, immune cell therapy and traditional chemotherapy cannot be carried out at the same time, but need to be alternated between the two.
16.Why is autologous CIK cell therapy likely to be superior to allogeneic sources?
Compared with allogeneic CIK cells, autologous-derived CIK has.
(1) To a large extent, immune cells that recognize tumor cells exist in the patient’s body and may have a recognition memory function. After being heavily expanded in vitro and then returned to the body, these immune cells may have the efficacy of targeted tumor recognition and killing.
(2) The CIK cells expanded in vitro come from themselves and will not “fight” with the unexpanded cells in the body after transfusion.
17.Is immune cell therapy only an adjunct to tumor treatment?
Immune escape or immune senescence is an important cause of many tumors. More and more clinical practice proves that immune cell therapy is an indispensable part of tumor treatment, rather than a “dispensable” adjuvant therapy to increase immunity in the traditional sense.
18.Introduction of DC preparation and treatment process.
The protocols adopted by each treatment institution may vary, but in our department
(1) Aseptically remove tumor tissue specimens of green bean to soybean size and send them to GLP operation room for freezing and storage.
(2) About 50 ml of peripheral blood is drawn from the patient and sent to the GLP operation room for DC culture preparation by dedicated personnel.
(3) Generally, DC vaccine sensitized by tumor cells can be prepared 7-10 days after blood sampling.
(4) The prepared DC suspension will be injected at multiple points along the superficial lymph nodes (the doctor will decide the injection site according to the location of tumor occurrence and metastasis).
19.Introduction of CIK culture and treatment process.
The protocol adopted by each treatment institution may vary, our department is.
(1) Depending on the patient’s leukocyte count, generally about 50 ml of the patient’s own peripheral blood is drawn.
(2) Send the cells to the GLP operation room for cell isolation, selection and culture, adding different amounts of cytokines and antibodies according to the cell growth, etc., and send them to a third party for quality control during the amplification of the culture.
(3) The time of transfusion is decided according to the maturity of the cells and the total amount of amplification, usually between 13-15 days after blood sampling.
(4) The physician determines whether the patient needs intramuscular injection of thymidine before blood sampling or interleukin 2 after transfusion.
20.Why do stem cells have the potential for disease treatment?
In addition to hematopoietic stem cell transplantation for malignant blood diseases, the use of stem cells for the treatment of various diseases is an important theme that has been explored and practiced by human beings in the last century, and has been of particular interest to all walks of life in the last decade. The universal characteristic of stem cells is their ability to differentiate in a variety of tissues, and this characteristic makes them have an optimistic prospect in tissue regeneration and disease treatment.
21.Prospects of clinical application of stem cells in disease treatment.
Among many different sources of stem cells, mesenchymal stem cells may be a kind of stem cells applied to the clinic on a large scale after hematopoietic stem cells, because this kind of stem cells have immunomodulatory, secretory effect and tissue trophic effects in addition to the differentiation potential of various tissue types. At present, there are many kinds of diseases treated with this kind of stem cells at home and abroad, such as graft-versus-host disease (GVHD) after bone marrow transplantation The use of such stem cells in the treatment of diseases such as graft-versus-host disease (GVHD) after bone marrow transplantation, diabetes mellitus, various immune system diseases, tumor chemotherapy support therapy, and various tissue regeneration has been widely used at home and abroad. Although the results of preclinical studies in the treatment of these diseases are superior to conventional treatments, they are still in the experimental clinical application stage.