Summary: Recent advances in immunotherapy based on autologous tumor-immersed lymphocytes (TIL).

The introduction of the famous immunotherapy of the last two years may have been known to many, but this is only the tip of the iceberg, although PD-1 has given some lucky late-stage patients a death-free gold medal.
but not desirable, PD-1 works only for 20% to 30% of patients; CAR-T therapy, while giving blood tumors "cure" hope, has not made a breakthrough in up to 90% of solid tumors.
researchers have been trying new types of immunotherapy to break the ice! Succession therapy is the body's immune cells in vitro induction, modification, amplification, screening out of the effect of the effective tumor killing activity with special high-efficiency cells back into the patient's body, inhibition and killing of tumora a therapy, media hot-fry CAR-T therapy is a kind of succession therapy.
follow-up tumor-immersed lymphocyte therapy is to expand tumor-immersed lymphocytes (TIL) in vitro screening and then back into the patient."
what is the tumor-soaked lymphocyte (TIL)? TIL refers to white blood cells that leave the blood stream and enter the tumor.
when there is a large amount of TIL, it indicates that the body initiates an immune response to the tumor.
these TilTs have immune cells specifically designed to deal with tumors, and if they are in vitro to increase their numbers substantially and then back into the patient, it is indeed an anti-tumor force.
declare war on solid tumors! TILs therapy shocked four of the most promising TILS (tumor-immersed lymphocytes) therapy in solid tumors for nearly two years, finally breaking this deadlock, for a variety of clinically incurable solid tumors have achieved amazing four clinical results.
last year's ASCO meeting, the clinical results of TilS cells-based innovative therapies LN-145 and LN-144 (Lifileucel) in the treatment of cervical cancer and melanoma attracted widespread attention in the medical community, where TIL treatment in melanoma has the potential to have a full response (CR) for decades, thanks to the persistence of memory T cells.
let's look at the progress that TILs therapy is making in various types of solid tumors.
1, TIL therapy extends PD-1 drug-resistant non-small cell lung cancer patients have the highest incidence and death of lung cancer in the world, although in recent years the development of targeted and immunotherapy has made lung cancer more and more chronic treatment, but for some patients, when the final substrate PD-1 drug resistance, still let patients panic.
april 27, AACR, at this year's AACR conference, a well-known U.S. cancer center, the Moffitt Cancer Research Center (H. The Phase I clinical results based on TIL cell therapy by Lee Moffitt announced that in 12 assessable patients with non-small cell lung cancer, TIL therapy achieved a total remission rate of 25%, two of whom achieved long-lasting total remission.
Despite the small size of the study, oncologists are heartened by the progression of their condition after being clinically treated with PD-1 (Opdivo), arguably the most difficult group of patients.
when the cancer-fighting tils cells are extracted from the tumor lesions of these patients and grown into billions of immune forces with precision-killing capabilities in vitro, and returned to fight in the body, most patients begin to see a significant tumor withdrawal after the first TIL treatment.
a total of 32 patients participated in the trial, and 16 patients were eventually treated with TILS, 12 of whom could be evaluated.
at an average follow-up of 1.4 years, three patients were relieved, two of whom were completely patients, and had been in the past year.
another patient's remission is about to be confirmed.
most patients received TILs treatment, the tumor lesions have shrunk, after treatment after the first CT scan, the tumor lesions diameter decreased by an average of 38%! Therefore, after PD-1 treatment, TILs therapy still has the ability to achieve long-lasting remission of advanced metastatic non-small cell lung cancer, which is very remarkable, i hope this therapy can increase research, early approval to market, for the life of advanced patients continue to survive! 2, Lifileucel brings spring to patients with advanced melanoma! Lifileucel (LN-144) is an immunotherapy for melanoma based on autologous tumor-immersed lymphocytes (TIL), developed by Iovance, a T-cell-based pass-by-cell therapy (ACT).
C-144-01 is a Phase 2 clinical trial that recruits patients who have been diagnosed with Phase IIIc or Stage IV metastatic melanoma.
patients must undergo at least one systemic treatment, including 66 patients treated with PD-1 inhibitors, 80 ctLA-4 inhibitors and 23 braF/MEK inhibitor combinations.
clinical trial is designed to determine whether TIL therapeutic therapy LN-144 is safe and effective in treating metastatic melanoma (helping patients extend life and/or slow cancer progression).
in the latest 66 patients with PD-1 treatment for advanced melanoma, the results showed that the disease control rate (DCR) was as high as 80%, the objective remission rate reached 38%, including 2 cases (3%), 23 partial remission (35%) and 28 cases (42%) were stable; More strikingly
, patients with PD-L1 negative also responded, suggesting that patients who were not effective with immunocheckpoint inhibitors could still benefit from TIL therapy.
for patients progressing after PD-1 treatment, there are few other treatment options, and the effect of this treatment is almost unparalleled.
a patient with advanced melanoma had extensive metastasis before treatment, the lesions were significantly reduced one month after treatment with TILs, 6 months of treatment reached full remission, remained in a state of complete remission after two years of treatment, and the tumor reactive CD8 plus T cells persisted in the body.
3, disease control rate 89%! Advanced cervical cancer LN-145 therapy won the FDA breakthrough therapy title! LN-145 is an automated tumor-immersed lymphocyte (TIL) therapy developed by Iovance, a T-cell-based secondary cell therapy (ACT).
data from the second phase of the active trial of innova TIL-04 (C-145-04), the overall response rate (ORR) of TIL treatment in patients with advanced cervical cancer was 44%.
27 assessable patients by the end of the year on February 4, 2019.
average injection of TIL cells: 28 x 109;
results show that the objective mitigation rate (ORR) is 44%, the total mitigation rate (CR) is 11%, and the disease control rate (DCR) is as high as 85%.
12 patients had an effect, including 1 full response, 9 partial responses and 2 unconfirmed partial responses;
is heartening, based on this clinical trial's stunning data, the FDA approved LN-145 for breakthrough treatment of advanced cervical cancer because, in patients with cervical cancer who progress edified during or after chemotherapy, the response rate for previously reported advanced cervical cancer chemotherapy or immunotherapy second-line therapy was only between 4% and 14%.
the new, very safe cell immunotherapy, which has a 44 percent response rate for patients with advanced cervical cancer and has shown lasting response in some patients, researchers say the treatment offers hope for long-term disease control.
hopes the treatment will be approved as soon as possible.
4, head and neck squamous cell carcinoma C-145-03 is a Phase 2 clinical trial that recruits patients with recurrent and/or metastatic HNSCC who have been treated with at least one previous form-auropathic and/or chemotherapy treatment. preliminary data
showed that three of the eight patients in the trial had a 30 percent reduction in tumor size.
5, solid tumor IOV-COM-202 is a Phase 2 clinical trial that recruits patients who have been diagnosed as heliologically non-removable or metastatic melanoma (queue 1), head and neck recurrence or metastatic squamous cell carcinoma (queue 2), or patients with relapses or metastasis (queue 3).
clinical trials designed to determine whether Iovance research TIL therapy (LN-144/ LN-145) is safe and effective in treating non-removable/metastatic melanoma, recurrent/metastatic HNSCC and NSCLC (to help patients live longer and/or slower to reduce cancer progression), and no clinical results have been published.
(progress of ongoing clinical studies) Deep Science: The Pre-Life 1, Pioneer-Immune World Taidoo Rosenberg Secondary T-Cell Therapy - TIL Cell Therapy is a new approach pioneered by the immune community' Tedo Rosenberg and his team.
, Grandpa is 78 years old this year, is a world-renowned expert in cancer and immunology, and is the director of surgery at the American Cancer Institute (NCI).
Rosenberg believes that when cancer cells invade, its immune system tries to beat the tumors that spread in the body.
for the past three decades, he and his team have been working on one thing: how to find and amplify the parts of the immune system that do the best job of "defeating" the immune system.
this is TIL-tumor-soaked lymphocytes. Steven Rosenberg (NCI) 2, TIL-the most lethal immune cell in the body , TIL-Tumoring lymphocytes, refers to tumor-soaked lymphocytes.
in the early stages of cancer, the immune system tries to attack tumors by mobilizing special immune cells from lymphocytes.
in surgically removed tumor tissue, we found that most of the tumor cells, but also a small number of lymphocytes.
some of these lymphocytes are T-cells that target tumor-specific mutation antigens, and Dr. Rosenberg believes they are the most powerful immune cells to strike inside the enemy, but for a number of reasons, such as tumor microenvironments and PD-1, their function is inhibited and their function is not effective in killing tumor cells in tumor tissue.
, however, scientists use some in vitro culture methods to enrich some type of lymphocytes in these tumor tissues and then return to the patient, which can play an anti-tumor effect, and the combined PD-1 effect is better.
3, 1988, the birth of the solid tumor of the lexin-TILs therapy 1986 in vitro studies showed that the human-derived TILs obtained from surgically removed malignant melanomas contained T lymphocytes that specifically identify autologous tumors, and when a large number of tumor-immersed lymphocytes were present, the body showed an immune response to the tumor.
these studies led Rosenberg to demonstrate for the first time in 1988 that the use of an inherited T-cell therapy with an autonomous TILs can lead to an objective tumor retreat in patients with metastatic malignant melanoma.
currently, ncI of the National Cancer Institute has been very successful in this area and has been treated at other major cancer centers, such as the Moffitt Cancer Center.
2011, a Phase 2 clinical study of metastatic melanoma published in clinical cancer research in clinical cancer research, published in the national cancer institute, showed that THE objective remission rate (ORR) for TIL treatment of melanoma patients was 56% and the total mitigation rate (CR) was as high as 24%.
and studies have shown that the number of immune cells immersed in tumors is proportional to the patient's chances of survival.
melanoma is one of the cancers with a relatively high mutation load, and tumors are run by these immune cells, and some patients involved in the early trials have responded to the treatment for more than a decade.
2019, the FDA awarded the tumor-immersed lymphocyte (TIL) treatment LN-145 as a breakthrough treatment, the first time cell immunotherapy for solid tumors has been awarded this award, and it is believed that it is only a matter of time before the FDA approves it, which will be the first cell immunotherapy for solid tumors, which will bring huge survival benefits to cancer patients.
4, how is TILs therapy different from other cell immunotherapy? Car-T, NK cell therapy for tumors is well known, and TIL is a completely different kind of new treatment from traditional cell therapy.
1. The more lethal TIL immune cells come from tumor tissue, while most of other cell immunotherapy is taken from the blood, which directly determines the ability of immune cells to recognize tumors.
estimates, more than 60 percent of the immune cells isolated in the tumor can identify the tumor, while less than 0.5 percent of the immune cells isolated in the blood.
. Finding specific mutations and accurately identifying this new type of therapy is not like the traditional simple amplification back transfusion, but rather the identification of specific mutations in a patient's case.
then used mutation information to find T-cells that were most effective at targeting these mutations, and finally extracted T-cells that specialize in cell mutations in patient tumors, which have the ability to accurately identify cancer cells.
Rosenberg's research on patients with common gastrointestinal cancers demonstrates the uniqueness of immune responses between patients.
identified 124 new antigen SYTs by sequencing biological samples from 75 patients.
they found that 83% (62) of patients cultured TIL were able to test 1.6 percent of somatic cell mutations expressed by body tumor cells.
99% of the new antigen decision clusters are completely different in every cancer patient.
therefore, cells must be taken from each cancer patient to determine which cells can actually identify and attack cancer, culture these cells, and amplify them to be therapeutic.