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There are great ways to fight tumors

2019-07-03
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In 2015, the 90-year-old former US President Carter unfortunately suffered from melanoma with brain metastases. After receiving comprehensive treatment including immunotherapy, the tumor in the brain miraculously disappeared. Against the background of the time, the emergence of this incident was like a ray of light in the dark, illuminating the dark road for people to fight tumors.
For a long time, humans have tried various methods to fight tumors, but due to various reasons, the effects of these methods have been unsatisfactory. In fact, the body’s immune system itself can recognize and eliminate mutant cells and maintain the stability of the body’s environment. However, in the process of tumorigenesis, tumor cells will escape the attack of lymphocytes in the body through various mechanisms (such as loss of antigen, loss of immunogenicity, and activation of inhibitory microenvironment). Tumor immunotherapy is the use of technology to reactivate the immune system so that it can recognize cancer cells and eliminate them.
Immunotherapy has completely overturned people’s previous concept of tumor treatment, from relying on external methods to kill tumors to relying on the autoimmune system to kill tumors. At present, tumor immunotherapy has become the fourth largest tumor treatment after surgery, radiotherapy and chemotherapy drugs, and it is also the most popular tumor treatment method.

 Tumor immunotherapy
Tumor immunotherapy

Methods of tumor immunotherapy

CAR-T

CAR-T is a bioengineered T cell. When the tumor patient has immunodeficiency and immune surveillance is not effective, the target of leukemia is determined by bioengineering technology, and it is specifically embedded in the T cell. Attacking leukemia cells has a significant effect, but it is prone to “cell storm”, which can even lead to death in severe cases. CAR-T is mainly based on cells targeting CD19, which has played an amazing therapeutic role in hematological malignancies and has been approved for marketing in the United States. CAR-T is processed in vitro, which can avoid multiple mechanisms of tumor immunity in vivo. However, the use of CAR-T in the treatment of solid tumors is more challenging. First of all, it is difficult to select specific targets for solid tumors. The choice of target is related to the adverse effects of CAR-T. If the target is not properly selected, off-target effects will occur, leading to more adverse reactions. Secondly, CAR-T is an activated T cell that needs to play a role in the tumor tissue. However, only 1% to 2% of the T cells injected into the body through the vein can reach the deep part of the tumor tissue, which is not enough to exert an effective anti-tumor effect. Third, after CAR-T enters the deep part of tumor tissue, it needs to overcome multiple obstacles in the tumor immune microenvironment to continue its anti-tumor effect.

 CAR-T cell therapy
CAR-T cell therapy

Immune checkpoint inhibitor therapy (PD-1, PD-L1, etc.)

Immune checkpoint inhibitor therapy has the advantage of making patients long-term survival and relatively small adverse reactions. This therapy activates tumor-specific immune cells in the body by removing or weakening the negative regulators of immune active cells. The most common adverse reaction of PD-1/PD-L1 is interstitial pneumonia or immune pneumonia. Immune enteritis can also occur. When it activates autoimmune response, it may also activate antibody response at the same time, but this adverse reaction is relatively Controllable.

 PD-1/PD-L1
PD-1/PD-L1

Immunotherapy is not suitable for all patients. The higher the mutation load of the patient, the better the response to treatment. Therefore, it is necessary to screen the dominant population through biomarkers. PD-L1, microsatellite instability (MSI), and tumor mutation burden (TMB) are the most mainstream predictive markers for PD-1/PD-L1 immune checkpoint inhibitors. In addition, immunotherapy can be used as an important anti-tumor adjuvant therapy besides chemotherapy, radiotherapy, and surgery. Appropriate immunotherapy can kill tiny residual tumor cells after chemotherapy or some tumor cells resistant to chemotherapy. Some patients cannot tolerate chemotherapy or have extensive metastases, and cannot undergo surgery, radiotherapy, or chemotherapy. They can consider immunotherapy.

Tumor vaccine

The treatment of tumor vaccines is still not perfect, because its audience belongs to a small group of people, and it is a local treatment, so the adverse reactions are not very clear.

Tumor vaccine
Tumor vaccine

Advantages and disadvantages of tumor immunity


Tumor immunity is characterized by slow onset, long time of action, and delayed effect. Once it takes effect, the symptoms will be improved lastingly, which can prevent recurrence. The emergence of immunotherapy not only revolutionized the standard of cancer treatment, but also revolutionized the concept of cancer treatment. It is known as the third revolution following traditional chemotherapy drugs and targeted tumor therapy.
Compared with traditional targeted therapy, the target must be targeted, and its toxicity cannot be ignored. It is ineffective for tumor cells without mutations, but tumor immunity does not. It kills tumor cells by improving the immune system. At the same time, compared with conventional treatments such as chemotherapy, tumor immunotherapy has significantly improved the frequency and severity of side effects. However, some serious and even life-threatening adverse reactions are not ruled out.
Although tumor immunotherapy has significant advantages, tumor immunotherapy kills tumor cells at a relatively slow speed. Currently, all immunotherapies used have different degrees of immune evasion, that is, activated immune cells cannot recognize tumor cells and reduce immunity. The effect of treatment. At the same time, tumor immunotherapy will also have side effects and adverse reactions during the treatment process, and the response rate is low, depending on the individual’s physical condition.

Opportunities and challenges faced by tumor immunotherapy

Immunotherapy is not the end point of tumor treatment. On the contrary, tumor immunotherapy represented by immune checkpoints has just opened a new chapter in tumor treatment. Combining with the basics and characteristics of immunotherapy, as humans’ understanding of tumors becomes deeper and deeper, tumors are no longer so remote as a chronic disease that can be cured.
However, while tumor immunotherapy brings vitality, it is also accompanied by many doubts and difficulties, such as how to choose the appropriate beneficiary group of immunotherapy drugs, how to overcome various adverse reactions and even side effects, and to further improve the efficacy. Given the opportunity and this Nobel Prize opportunity, I firmly believe that tumor immunotherapy has a future, which will bring more surprises and hopes to tumor treatment.

About Medicilon

Medicilon is a drug research and development outsourcing service company (CRO), which has established a compound synthesis, compound activity screening, structural biology, pharmacodynamic evaluation, pharmacokinetic evaluation, toxicological evaluation, formulation research and new drugs in Shanghai. Registered as an integrated technical service platform that meets international standards, and has been recognized by the international drug administration. Medicipua’s animal laboratory facilities have obtained AAALAC (International Association for Animal Evaluation and Certification) certification and China Food and Drug Administration GLP certification, and have reached the US Food and Drug Administration GLP standard. Medicilon helps customers reach their goals faster with efficient and cost-effective one-stop professional services.
Medicilon has rich experience and effective animal models in the evaluation of anti-tumor drugs. More than 200 tumor evaluation models have been established for the evaluation of the efficacy of anti-tumor drugs, including xenogeneic tumor transplantation models, orthotopic tumor transplantation models, and homologous tumor models. Tumor transplantation models, genetically modified mouse tumor models, humanized tumor transplantation models, and the use of radiotherapy and chemotherapy combined treatment evaluation technology, can treat cytotoxicity and target small molecule drugs, monoclonal antibodies and bispecific antibodies and other macromolecular drugs, ADC , CAR-T cell therapy new anti-tumor drugs provide a comprehensive and systematic evaluation.

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