2022 CSCO | Professor Wang Baocheng: Heading to heights, exploring the unknown, and looking forward to immunotherapy unlocking more surprises

preface

The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
from November 5th to 12th.
The theme of this conference is "Precision Innovation, Intelligent Humanities", the conference focuses on the clinical frontier of oncology, joins hands with experts and scholars in the field of oncology across the country, shares clinical research and innovation results, and strives to comprehensively and accurately reflect new concepts and new trends
in the field of clinical oncology.
During the CSCO Annual Meeting on immunotherapy held in Jinan on November 6, Yimaitong specially invited Professor Wang Baocheng of the 960th Hospital of the People's Liberation Army to share the cutting-edge progress
of immunotherapy with us.

- Professor Wang Po Shing -

Chief physician, doctoral supervisor

Vice President of the 960th Hospital of the People's Liberation Army (formerly the General Hospital of Jinan Military Region).

Former director of the Institute of Oncology of Jinan Military Region

Standing Director of Chinese Society of Clinical Oncology (CSCO).

Chairman of the CSCO Immunotherapy Committee

Member of the Standing Committee of the CSCO Antitumor Drug Safety Management Expert Committee

Member of the Standing Committee of the CSCO Liver Cancer Expert Committee

Member of the CSCO Malignant Melanoma Expert Committee

Vice Chairman of the All-Army Oncology Professional Committee

Health consultation expert of the Central Military Commission

Vice President of Shandong Medical Doctor Association

Director of the National Drug Clinical Validation Agency

Editor-in-Chief of Chinese Journal of Gastroenterology and Imaging, etc

Yimaitong: With the wide application of immunotherapy in the clinic, immunotherapy resistance has gradually become a clinical problem that needs to be solved urgently.

Professor Wang Baocheng

PLA 960th Hospital

Immunotherapy has been widely used in clinical practice, but immunotherapy resistance is inevitable
.
There are three main modes of resistance in immunotherapy: first, primary drug resistance, that is, the tumor does not respond to initial immunotherapy; The second is adaptive drug resistance, which means that although the tumor can be recognized by the immune system, but some mechanisms adapt to immune killing, thereby mediating immune resistance; The third is acquired drug resistance, that is, immunotherapy is effective in patients at first, but after a period of treatment, the efficacy gradually decreases, and patients have disease recurrence or metastasis
.

Solving immunotherapy resistance requires us to have a deep understanding of the mechanism of drug resistance, know ourselves and others, and only then can we survive the battle
.
The drug resistance mechanism of immunotherapy mainly considers the following factors: first, the internal factors of the tumor, including the loss of tumor-specific antigen expression, antigen presentation defects, etc.
, and the change of signaling pathway will also lead to drug resistance; Second, the external factors of the tumor, the decline of immune cell function in the tumor microenvironment, the increase of immunosuppressive cells or molecules, etc.
; The third is host-related factors, including the patient's physical state, immune status, previous comorbidities, intestinal flora distribution, and antibiotic or hormonal drug use
.
The exploration of the mechanism of immune resistance will provide a theoretical basis
for the treatment strategy after drug resistance.

The treatment methods after immunoresistance need to comprehensively evaluate the patient's tumor status and immune status, deeply analyze the mechanism of drug resistance, and consider the treatment strategy
after drug resistance from different perspectives.
Screening of the immunotherapy-appropriate population is first needed to avoid primary resistance
.
Secondly, for the weakening or loss of tumor antigen expression, immune enhancers, such as the latest personalized tumor vaccines and oncolytic viruses, have been shown to enhance immune function
.
In addition, combination therapy strategies are important measures to delay or reverse immune resistance, and various combination treatment regimens (such as combination with other types of immunotherapy drugs, targeted drugs, antiangiogenic therapy, and chemotherapy) are important strategies
to improve immune efficacy.
The development of a new generation of new anti-tumor drugs is also one of the important ideas to overcome immune drug resistance, including new immune checkpoint inhibitors, oncolytic viruses, cellular immunotherapy, etc
.

It should be noted that in clinical practice, we have proposed an eight-character policy for anti-tumor treatment resistance - "if the effect is not changed, the ineffective must be changed", that is, after the emergence of drug resistance, the drug should be changed or stopped, but this policy is not applicable to immunotherapy
.
Studies have shown that patients who continue their current immunotherapy regimen for more than six weeks after the progression of immunotherapy disease can still benefit
from it.

All in all, there are many strategies for immune resistance, and targeted treatment can be given according to the type of resistance of patients, but there is still a big gap to meet clinical needs, and there is still a long way to go to overcome immune resistance
.

With the deepening of research on the mechanism of tumor immune escape, various new immunotherapies have come out
one after another.
From the current research progress, which emerging immunotherapies are promising?

Professor Wang Baocheng

PLA 960th Hospital

Immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors have made breakthroughs in tumor immunotherapy, bringing survival benefits to tumor patients and changing the pattern
of tumor treatment.
How to expand the patient population benefiting from immunotherapy and further improve the efficacy of tumor immunotherapy is the focus
of current research.
The search and development of new targets has never stopped, and new immune checkpoint inhibitors represented by TIGIT, LAG3, TIM3 and other targets have emerged
.

Oncology vaccines are also a hot spot
in current research and development.
Oncology vaccines include therapeutic vaccines and preventive vaccines
.
Therapeutic tumor vaccine refers to the purpose of controlling and treating tumors by injecting tumor-related antigens extracted from tumor tissues or human body fluids into tumor patients to activate the specific immune response of the body's immune system to kill tumor cells
.
The preventive tumor vaccine is mainly used to prevent tumorigenesis
.
Because the formation of malignant tumors is affected by many factors, the development of preventive vaccines is difficult
.

Oncolytic viruses are considered one of
the most promising cancer treatments because they can specifically replicate within tumor cells and cause tumor cell lysis without affecting normal cells.
In 2005, China approved the first oncolytic virus for the treatment of head and neck tumors, and up to now, a number of oncolytic viruses
have been approved at home and abroad.
There are more than a dozen domestic oncolytic virus clinical trial research projects, and ten related submissions have been accepted at this CSCO meeting, and various combination therapies based on oncolytic viruses are the current research hotspots
.

Immune cell therapy has broad application prospects in anti-tumor, including CAR-T cell therapy, CAR-NK cell therapy, etc
.
CAR-T has achieved remarkable results in the treatment of hematological malignancies, and has also inspired more and more scholars to expand this technology to solid tumors, but it will take time to truly apply it to the clinic
.
Developing more targets for CAR-T therapy, optimizing the CAR-T preparation process and saving costs, especially the promotion of universal CAR-T therapy are important research directions
.
In addition, CAR-T combination therapy is also expected to break through its dilemma
in solid tumors.

Through the tireless efforts of scientists and clinicians, immunotherapy is moving
forward at a speed that does not shift by human will.
I believe that with more and more research, immunotherapy will definitely bring us more surprises
.

Yimaitong: In the process of immunotherapy, the safety of drugs is also one of
the focuses of clinical attention.
The management of immune-related adverse reactions (irAEs) requires multidisciplinary collaboration, what are the key points in the management of irAEs?

Professor Wang Baocheng

PLA 960th Hospital

The safety and effectiveness of tumor immunotherapy are like two wheels of a carriage, and one is indispensable
.
Then, the key points of irAE management mainly include the following aspects:

First, doctors need to recognize and understand the characteristics and toxicity of immunotherapy to avoid being helpless in the event of severe or even fatal irAEs, resulting in irreversible consequences
.

Second, before applying immunotherapy, the patient needs to be initially screened, assess the patient's physical condition, and identify immune-related risk factors to determine whether the patient is suitable for immunotherapy
.

Third, closely monitor the occurrence of irAE, which requires medical staff and patients' families to report abnormalities in a timely manner, so as to facilitate early detection, accurate diagnosis and accurate treatment
.

irAE can occur in almost every tissue and organ, and can be divided into common and rare toxic reactions, mild, moderate and severe toxic reactions, reversible and irreversible toxic reactions, etc.
, which require comprehensive judgment
by clinicians.
The management of irAE requires graded assessment, generally speaking, grade 1-2 irAE symptoms are mild, and symptomatic supportive care measures are sufficient; For severe irAEs of grade 3 and above, patients should be hospitalized and discontinued, and consultation and treatment
should be conducted by a multidisciplinary team.

Whether immunotherapy can be restarted after severe irAE is also a topic
of great concern to clinicians.
The CSCO Guidelines for the Management of Toxicity Related to Immune Checkpoint Inhibitors states that the patient's tumor response status is an important factor
in deciding whether to restart immunotherapy.
In view of the continuous expansion of the population adapted to immunotherapy, in-depth understanding of irAE will help patients to maximize the benefits from immunotherapy, so the use of big data for irAE research can help to discover the biomarkers of irAE and clarify the correlation between irAEs and immune benefits, which is an important research direction
in the future.

Edited by Faline

Reviewer: Professor Wang Baocheng

Typesetting: Faline

Execution: Uni

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