Lung cancer is the malignant tumor with the highest incidence and mortality rate in the world, with morbidity and mortality rates accounting for 11.6% and 18.4% of all tumors respectively. Among them, non-small cell lung cancer (NSCLC) patients account for about 85%, and the survival rate of advanced patients in the past five years was about 5%.
Platinum chemotherapy has always been the standard first-line treatment for advanced non-small cell lung cancer. However, the toxicity and side effects of chemotherapy can affect patients' physical health and quality of life, and the treatment effect is limited and has not developed much in the past decade. Although the treatment of non-small cell lung cancer has improved with the development of targeted drugs in patients with corresponding mutations, only a small number of tumors have these mutations, and most tumors will become resistant to targeted treatments.
In the past two years, immune checkpoint inhibitors are undoubtedly one of the most successful tumor immunotherapy, which has changed the treatment prospects for lung cancer. In the chemotherapy era, the five-year survival rate of in patients with advanced lung cancer is extremely low, only about 5%. Data shows that some types of lung cancer patients use immunotherapy for , and their five-year survival rate can be as high as 31.9%, a 6-fold increase! This undoubtedly brings "gold medals to avoid death" to more patients.
But unsatisfactory, PD-1 only works for 20% to 30% of patients, and the moderate to severe side effects are as high as 30%. How to enable more patients to benefit from immunotherapy and how to further improve the effectiveness of immunotherapy is the direction that oncologists are actively exploring now and in the future.
In the past two years, many cutting-edge lung cancer therapies have been emerging. From September 9 to 13, the latest progress on spot tumor neoantigen vaccine was announced at the 2022 European Society of Oncology Annual Meeting (2022ESMO).
Survival period of patients with advanced lung cancer has doubled! Spot tumor vaccine allows patients to live longer
announced the results of the clinical phase 1/2 trial of the SLATE-KRAS and SLATE v1 cancer vaccine project in the treatment of patients with advanced solid tumors at the 2022 ESMO Conference held recently. Both projects are spot-based, targeted common tumor neoantigens vaccines. The study found that the combination of this therapy with immune checkpoint inhibitors can achieve positive therapeutic effects and demonstrate good safety.
screenshots are from Gritstone bio official website
SLATE project is a cancer vaccine immunotherapy that uses engineering methods to deliver tumor neoantigens into patients' bodies to stimulate T cell responses (especially CD8+ poison T cells) to attack tumors. The SLATE v1 developed under this project can produce up to 20 common tumor neoantigens produced in proteins such as KRAS, TP53, β-catenin, BRAF, etc. The SLATE-KRAS project developed for specifically targets KRAS-related neoantigens, including G12C, G12D, G12V, and Q61H driver mutations commonly found in patient tumors.
In the clinical phase 1/2 clinical trial, 38 patients with metastatic solid tumors with specific KRAS mutations were selected and entered the SLATE v1 (n=26) and SLATE-KRAS (n=12) cohort respectively, aiming to test the early clinical effect and safety of SLATE v1 and SLATE-KRAS combined with the PD-1 immune checkpoint inhibitor nivolumab and the CTLA-4 antibody ipilimumab.
It is worth mentioning that 81.6% (31/38) of patients are advanced non-small cell lung cancer (n=18) or microsatellite-stable colorectal cancer (n=13).
clinical trials show that these two vaccines show strong immunogenicity , and 31% and 55% of patients treated with SLATE v1 and SLATE-KRAS trigger KRAS-specific CD8+ T cells, respectively.
When the treatment effect (molecular remission) was examined by measuring the circulating tumor DNA (ctDNA) content in the patient's body, it was found that in patients with microsatellite-stable colorectal and non-small cell lung cancer that could be tested, achieved molecular remission (decreased ctDNA content).
In 18 patients with non-small cell lung cancer, achieving molecular remission was associated with prolonged overall survival. The median overall survival of non-small cell lung cancer patients who achieved molecular remission was 9.6 months , while that of 4.5 months was not achieved molecular remission.
This therapy has good safety and tolerance. Most of the treatment-related adverse reactions are grades 1 and 2, which are mild.
In the development project of this tumor vaccine, the early efficacy shown by SLATE-KRAS is encouraged. is mainly aimed at in patients with advanced and refractory cancer, and is a product that targets multiple KRAS mutations. has a molecular remission in approximately 40% of patients receiving SLATE, which is associated with the extended overall survival observed in patients with non-small cell lung cancer, showing the broad therapeutic potential of this cancer vaccine.
How to seek personalized cancer vaccine treatment
At present, the most outstanding efficacy and prevention of recurrence in cancer vaccines is Dendritic cell vaccine Dendritic cell vaccine and personalized neoantigen vaccine , etc. In Germany and Japan, dendritic cell vaccines are also used to treat a variety of cancers, such as lung cancer, liver cancer , kidney cancer , breast cancer , skin cancer , etc. This is the new hope for cancer patients to treat.
Patients who want to seek new treatment technologies at home and abroad, . Under economic conditions, they can first submit the pathological report, treatment experience, discharge summary and other information to Cancer-free Home School of Medicine 4006269916 for preliminary evaluation.
NEO-PV-01 vaccine "shot three times in one stone" to continuously destroy lung cancer, bladder cancer , and melanoma, significantly prolonging the survival period
1Neon developed NEO-PV-01 is a "tailored" individualized neoantigen vaccine. extends progression-free survival in patients with melanoma, non-small cell lung cancer (NSCLC) and bladder cancer in early clinical trials. This result reveals the potential of an innovative immunotherapy model for cancer vaccines.
This study was published in the 2020 journal Cell. The study presented the results of the Phase Ib clinical trial of the first developed-labeled tumor personalized neoantigen vaccine NEO-PV-01 combined with PD-1 antibodies for patients with advanced melanoma, non-small cell lung cancer or bladder cancer.
This trial is open to patients with unresectable or metastatic melanoma, smoking-related non-small cell lung cancer, and bladder urothelial cancer, and recruits subjects at 9 major cancer centers in the United States.
It is understood that the NEO-PV-01 vaccine is customized based on the unique tumor gene mutation points of each patient. The principle is that after injects NEO-PV-01 into the human body, it can activate T cells in the human body and produce an anti-tumor immune response, thereby killing tumor cells.
During the vaccine production period, the patient first received nivolumab for 12 weeks; after 12 weeks, the patient began to inject NEO-PV-01 subcutaneously. Five initial immunizations and two booster immunizations were performed over three months, which constituted a complete NEO-PV-01 treatment cycle.
clinical data show that
9 clinical centers recruited 82 subjects who had received at least one dose of nivolumab, of which 60 patients received vaccine treatment, including 27 melanoma, 18 non-small cell lung cancer, and 15 bladder cancer.
As of August 2019, based on data after at least 12 months of follow-up, the researchers analyzed:
1. Objective response rate:
1. Objective response rate:
Melanoma: 59% (39%~78%);
Non-small cell lung cancer: 39% (17%~64%);
Bladder cancer: 27% (8%~55%)
2. Median progression-free survival:
melanoma: 23.5 months;
non-small cell lung cancer: 8.5 months;
bladder cancer: 5.8 months
3. Overall survival rate within 1 year:
Melanoma: 96% (76%~99%);
Non-small cell lung cancer: 96% (76%~99%);
bladder cancer: 67% (38%~85%)
Historical data shows that nivolumab single-drug treatment, achieved PFS in melanoma patients is 3 to 7 months, 2 to 4 months in non-small cell lung cancer patients, and 2 to 3 months in bladder cancer patients. The trial results show that compared with historical data on and nivolumab monotherapy, combined therapy significantly prolonged survival in all three cancer patients.
lung cancer vaccine PD-1-Vaxx combined with atelizumab can reduce some immune resistance! Primary or secondary resistance caused by
After treatment with PD-1/PD-L1 monoclonal antibody has always been a difficult problem that needs to be solved urgently. PD-1 chimeric B-cell peptide epitope vaccine IMU-201 (PD1-Vaxx) can induce the production of polyclonal antibodies in vivo that can block PD-1 signaling, thus having anti-tumor effects similar to immune checkpoint inhibitors. It also induces memory T and memory B cell responses, reducing immune escape and immunosuppression of tumor cells.
IMU-201 trial selected non-small cell lung cancer patients with PD-L1 expression, had previously received ICIs treatment, and had disease progression as the research subjects.
In the Phase I stage, 4 patients were recruited in the IMU-201 10 μg dose group, 50 μg dose group and 100 μg dose group, and no dose-limiting toxicity was observed.
In the 10 μg dose group, was completely relieved and 1 case of stable disease.
In the 50 μg dose group, disease was stable in 4 cases.
In the 100 μg dose group, partially relieved 1 case and 2 cases of stable disease. In theory, the clinical drug resistance problem of some immune checkpoint inhibitors can be overcome in combination with the combination of lung cancer vaccine and PD-1 antibodies. The results of this study show preliminary safety and efficacy, and will now enter Phase Ib to evaluate the efficacy of IMU-201 combined with atetirizumab. Let us wait and see.
What is the neoantigin of tumor? New breakthrough in tumor immunotherapy !
What we just mentioned earlier is a personalized neoantigen vaccine. The editor of Cancer-Free Home is here to popularize a new concept of immunotherapy: Neoantigen (neoantigen). As we all know, cancer cells are transformed from normal cell cancer and are originally part of the human body. They just cannot withstand the temptation of "sugar-coated cannonballs". When they become corrupt and degenerate, they will lurk in the human body and "disguise" into normal cells, trying every means to mislead the defense mechanism. If they successfully avoid the pursuit of the defense mechanism, cancer cells will take root in normal tissues. After a long period of development, they will eventually form cancer.
However, for normal cells to become cancerous, they must accumulate enough oncogenic mutations. The oncoprotein produced by these oncogenic mutations is unique to cancer cells and does not exist on normal cells. and tumor neoantigens are specific antigens produced by mutations in cancer cells. They are not expressed in normal cells and can activate CD4+T and CD8+T cells to produce immune responses and inhibit tumor growth; has high immunogen , long antitumor immunity, and is not easily tolerated; its target is tumor specific antigen (TSA), which only kills cancer cells and is an individualized precision cell immunotherapy.
Source: "New Progress in Research on Tumor New Antigen Vaccine"
The most critical step in designing a tumor vaccine is to find the correct antigen . tumor antigens are traditionally divided into tumor-associated antigens (TAAs) and tumor-specific antigens (TSA) . tumor-associated antigen is a class of antigens that express simultaneously on both tumor cells and normal cell surfaces. Due to the need for growth, tumor cells may overexpress certain antigens on their surface, and this difference in expression levels will give patients a certain "treatment space". Therefore, by identifying and attacking this type of antigen, can also achieve the effect of "killing more enemies and hurting less yourself".
and tumor-specific antigen as the name suggests, and some antigens unique to tumor cells can accurately kill cancer cells in the tumor microenvironment through immune response without causing side effects of accidentally damaging normal cells. Therefore, antigens such as should be the most ideal target for tumor immunotherapy.
Cancer vaccine is an active immunotherapy and an important part of the field of tumor immunotherapy. It prevents cancer from developing or killing existing tumors by stimulating or restoring the human body's own immune system. cancer vaccine mainly includes cell vaccine, DNA vaccine, mRNA vaccine, polypeptide vaccine, dendritic cell vaccine, nanovaccine, etc.
In addition to the HPV vaccine is a well-known preventive cancer vaccine, Provenge (sipuleucel-T) is the only prostate cancer immunotherapy approved by FDA, which has since opened a new era of tumor immunotherapy. The biggest advantage of
neoantigen vaccine: "tailor-made" according to the patient's tumor tissue mutation antigen
Individualized neoantigen vaccine is based on gene sequencing, and individualized "high-end customized" vaccine with different mutation sites and multiple loci in each patient.
Compared with traditional vaccines, the biggest advantage of individualized neoantigen vaccine is that traditional vaccines are subject to the dual restrictions of HLA (human leukocyte antigen) and antigen expression, and patients who apply vaccines are limited; Individualized neoantigen vaccine is a "tailored" vaccine for each patient's tumor tissue mutation antigen. Even if it is still affected by the restriction of HLA in patients, it can ensure that each patient has its own specific vaccine and can be included in tumor patients to the greatest extent. can stimulate the autoimmune system to attack tumor cells, allowing more patients to benefit from individualized treatment in the long term.
The four basic steps in the preparation of neogenic antigen cancer vaccine are to obtain tumor tissues and normal cells, put forward new tumor antigens, determine new epitopes, and prepare vaccines. With the increasing maturity of neogenic antigen screening technology, a variety of neogenic antigen vaccines have entered the clinical trial stage. In the clinical trials of individualized neogenic antigen vaccines that have been carried out, involves more than 40 solid tumors, including melanoma, brain glioma, lung cancer, bladder cancer, pancreatic cancer , liver cancer, ovarian cancer, etc.
In addition to using active immunotherapy like cancer vaccine to prevent recurrence, another way to prevent recurrence is to use Adoptive Cell Transfer Therapy (ACT), which is passively immune to .It refers to the isolation of immune active cell from the tumor patient, amplification and functional identification in vitro, and then infusion to the patient, so as to directly kill tumors or stimulate the body's immune response to kill tumor cells.
In fact, there are many types of cell immunotherapy such as this that prevent relapse, such as NK cell therapy, dendritic cell vaccine, CTL therapy, and compound immune cell therapy.
NK cell therapy
In addition to CAR-T therapy, we also have the familiar NK cells (natural killer cells), which have great potential in tumor immunotherapy. NK cell strategies currently used for tumor immunotherapy include: in vitro activated autologous or allogeneic NK cell therapy; combined with NK cells and monoclonal antibodies (such as immune checkpoint inhibitors) to induce antibody-specific cytotoxicity; and construct CAR-NK cell immunotherapy.
CTL (cytotoxic T lymphocytes) therapy
For the vast majority of patients with inoperable advanced cancer, what cell therapy can be used as an auxiliary treatment?
In recent years, researchers have been developing new immunotherapy solutions for these patients, including CTL (cytotoxic T lymphocytes), namely cytotoxic T lymphocytes. This technology mainly uses protein unique to cancer cells, which does not have or are very low in normal cells as bait, and selects the "one in a thousand" lymphocytes that can truly fight cancer in peripheral blood, and then further improves and amplifies them in vitro, and then returns to the patient.
MTCA-CTL immunotherapy is a new generation of biological immunotherapy model launched in China. While ensuring the expansion of non-MHCh restriction killer NK-T cells, the MHC-restricted CD8+ specific CTL cells are targeted to amplify the ratio in cellular products to reach 60% to 70%. The combined effect of this killer cell makes the killer tumor cells more efficient.
complex immune cells
This technology simultaneously activates 6 types of cells including γδT cells, NK cells, NKT cells, killer T cells, dendritic cells and helper T cells , proliferating 10 to 20 million cells to 2 to 5 billion, and then inject them into the patient's body. Cultivating such important immune cells simultaneously greatly improves the therapeutic effect compared with treatment alone.
In addition to some leukemia and malignant lymphoma , it can be used for the treatment of most cancers and has good results in difficult-to-treat cancer types and middle- and advanced cancers.
In addition, compound immune cells are also very helpful in improving immunity and strengthening the body.
How to seek CAR-T and TCR-T cells for treatment
. For patients with middle and late stage solid tumors who fail standard treatment in can also consider using CAR-T therapy and TCR-T therapy for treatment.
Currently, recruitment of cancer-free homes is underway. Patients who want to participate can submit pathological report, treatment experience, discharge summary and other data to Cancer-free homes Department of Medicine tentative evaluation of the condition.
The editor has something to say
So, when a tumor patient is diagnosed, don’t panic, look for authoritative tumor experts or medical institutions, learn about your condition in detail, and treat it symptomatically. You cannot believe in folk remedies, and you cannot believe that health care products can treat cancer. A regular tumor hospital and authoritative tumor experts are the most correct choice for cancer patients!
This article is an original cancer-free home
