"We investigated the safety and efficacy of dendritic cell vaccine DCVAC/LuCa combined with standard carboplatin/pemetrexed in non-squamous non-small cell lung cancer.
Combination therapies showed good tolerance in selected Chinese populations.
The 2-year survival rate of the improved intended treatment population (n = 44) was as high as 52.57%. ”
In the past two years, targeted and immunotherapy has changed the treatment prospects of lung cancer. However, it is not satisfactory that many patients do not have relevant mutation targets and biomarkers, and drug treatment options can only choose traditional chemotherapy, so how to further improve the effectiveness of chemotherapy is the direction that oncologists are actively exploring now and in the future.
Recent studies have found that dendritic cells are the most powerful antigen-presenting cells in the body known today, and the biggest feature is that they can stimulate the proliferation of initial T cells. Therefore, DC is the initiator of the body's immune response and has a unique position in the induction of the immune response. Dendritic cells can kill tumor cells through a variety of mechanisms, and researchers wonder if combining dendritic cells with chemotherapy will be better?
This idea has been continuously confirmed in the clinical data published in the past two years! Dendritic cells combined with chemotherapy may become a new choice for the first-line treatment of advanced lung cancer!
The overall relief rate has increased dramatically! Dendritic cells combined with chemotherapy are dawning!
DCVAC/LuCa is a dendritic cell vaccine developed by a biological company called SOTIO in the United States for patients with non-small cell lung cancer. By fusing dendritic cells with antigenic substances released by autologous lung cancer cells after lysis and death, dendritic cells gain the ability to recognize lung cancer cells, and after in vitro expansion, they are reinfused back into the patient for treatment.
In a study of first-line treatment options for advanced lung cancer presented at ASCO 2019, researchers selected 112 patients from 12 research centers.
The results show:
mOS (median overall survival): 15.5 months for patients receiving DCVAC/LuCa combined chemotherapy and 11.8 months for patients receiving chemotherapy alone;
mPFS (median progression-free survival): 6.74 months for patients receiving DCVAC/LuCa combination chemotherapy and 5.63 months for patients receiving chemotherapy alone.
ORR (Objective Response Rate): The overall response rate was 45% for patients receiving DCVAC/LuCa combination chemotherapy and 34% for patients receiving chemotherapy alone.
Overall, DCVAC/LuCa reduced the risk of death for patients with stage IV non-small cell lung cancer by a whopping 46%! The results of this study provide evidence for the efficacy of dendritic cell vaccines in the treatment of non-small cell lung cancer. Researchers believe that on the basis of first-line standard chemotherapy regimens combined with dendritic cell therapy DCVAC/LuCa, the efficacy is definite.
Recently, the good news has come again, which is worth cheering for Chinese patients!
This US forward-looking therapy has been conducted in a phase II clinical study at Shanghai Chest Hospital, a well-known cancer center in China, to explore the safety and efficacy of the novel dendritic cell vaccine DCVAC/LuCa (lung cancer dendritic cell vaccine) combined with standard carboplatin/pemetrexed in the treatment of advanced non-squamous cell (nsq) non-small cell lung.
Experimental design
For stage IV non-squamous non-small cell lung cancer without genetic mutations that has not been previously treated, up to 6 cycles including carboplatin/pemetrexed are received, followed by 21 cycles of pemetrexed maintenance therapy or until disease progression or intolerance. It is important to note that patients who do not progress after two chemotherapy cycles begin dendritic cell therapy DCVAC/LuCa on day 3 and receive up to 15 doses every 3 weeks (day 15 of the chemotherapy cycle).
The results are very exciting!
Enrolled 61 patients and had a 2-year survival rate of 52.57% in the modified intended treatment population (n = 44). At the time of publication, the median total survival (OS) had not been reached. The median progression-free survival (PFS) was 8.0 months and the objective response rate (ORR) was 31.82%.
Overall survival and progression-free survival curves in the (A,B) mITT population. (C, D) Comparison of overall survival and progression-free survival of patients receiving DCVAC/LuCa > 8.95 × 106 DCs per≤ dose and 8.95 × 106 DCs per dose of DCVAC/LuCa.
Note: DC, Dendritic Cells; DCVAC/LuCa, Dendritic Cell Vaccine for Lung Cancer; mITT, Modified Intentional Therapy.
Therefore, it can be confirmed that the dendritic cell vaccine DCVAC/LuCa combined with pemetrexed and carboplatin showed good tolerance and promising efficacy in the treatment of patients with stage IV NSCLC without carcinogenic drivers, with no serious or unexpected adverse reactions, indicating that it is safe and feasible in selected Chinese populations. Although os data have not yet been conclusively determined, this therapy has shown synergistic effects and significant potential in improving patient survival.
Currently, the DCVAC/LuCa combined pemetrexed and carboplatin regimens will continue to be studied on immunotherapy concepts in a randomized Phase III trial. For more information, please call the Global Oncologist Network Medical Department. Related Reading: Dendritic Cell-Based Cancer Immunotherapy Handbook (2021 Patient Edition)
Treatment flow of DCVAC/LuCa dendritic cell vaccine
1. Blood collection, isolation of monocytes;
2. Prepare lung cancer cell lines and inactivate them with high hydrostatic pressure;
3. Immature dendritic cells are mixed with inactivated tumor cells to induce dendritic cell maturation;
4. Prepare mature DC 15 dose DCVAC/LuCa, frozen
5. The patient receives DCVAC treatment
About dendritic cells
Dendritic cells are known to be highly functional antigen-presenting cells in the body, and the biggest feature is that they can stimulate the initial T cells to proliferate. Therefore, DC is the initiator of the body's immune response and has a unique position in the induction of the immune response. Dendritic cells can kill tumor cells through a variety of mechanisms:
1 Dendritic cells present a large number of tumor antigen peptides by surface enriching MHCI and Class II molecules, so that the corresponding T cell receptors are fully occupied;
2 Dendritic cells provide high levels of B7-1, B7-2, CD40 co-stimulating factors, fully activating T cells;
3 Dendritic cells bind to T cells and secrete a large amount of IL-12, which is conducive to the clearance of tumors by T cells;
4 Dendritic cells simultaneously secrete chemokines, specifically chemotaxis naïve T cells, promote T cell enrichment, and enhance T cell activation.
Although the body's immune system originally has such dendritic cells, the number and vitality are not enough to annihilate the cancerous cells. So, after extensive research, researchers isolated precursor cells that had the potential to become dendritic cells by specific methods. With the help of a specific messenger, cells isolated in a test tube can acquire immunity. When somatic cells mature into dendritic cells, they can capture specific tumor antigens and effectively kill cancer cells.
And in vitro reconstructed dendritic cells can activate resting T cells to produce primary immune response cells when they are reincarnated back into the body, and activated T cells can be punctately scaled up and further proliferated. A dendrite can activate 100 to 3,000 T cells, some T cells quickly exert a huge anti-cancer effect, while the other part will survive for more than ten to decades to become memory T cells, the next exposure to low-dose antigens can occur high-intensity immune response. Therefore, the immune defense system based on dendritic cell repair and reconstruction can continue to function for decades and can re-enter the cycle under the right conditions to exert a long-term anti-cancer effect.
Since the anti-tumor properties of dendritic cells are consistent with the principle of vaccines, dendritic cell therapy is more called dendritic cell vaccine in the clinic.
At present, most of the global research on dendritic cells is in the early clinical trial stage, and we expect to see more valid data. Although current medicine cannot cure cancer, there have been many new research and treatment options such as the above-mentioned dendritic cell combination chemotherapy, which can improve the survival of patients and prolong survival as much as possible. We look forward to the early approval of these exciting new therapies for the benefit of more patients."