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What is TIL?

TIL, Tumor infiltrating lymphocytes refer to lymphocytes that infiltrate into the tumor microenvironment, mainly composed of CD8+T cells, CD4+T cells, gamma delta T cells, B cells, NK cells, etc. The TIL therapy refers to the treatment of isolating tumor infiltrating lymphocytes from tumor tissue, culturing and amplifying them in vitro, and reintroducing them back into the patient's body. The high heterogeneity of solid tumors makes it difficult to find ideal targets for all tumor cells, and therapies targeting a single tumor antigen often result in poor efficacy due to antigen loss. The anti-tumor components in TIL are polyclonal and multi-target T cells, which can effectively respond to the highly heterogeneous characteristics of solid tumor antigens; By amplifying and reintroducing these polyclonal T cells that have the ability to recognize and kill tumor cells from within or near the tumor into the patient's body, the immune response can be amplified and the tumor killing effect can be enhanced. The main mechanism is as follows:

① Direct killing: T cells recognize tumor antigen peptides presented by MHC-I molecules on the surface of tumor cells through TCR, releasing perforin and granzyme. After being released in monomeric form, perforin is inserted into the tumor cell membrane to form tubular polymeric perforin (pores), which can allow Na+and water molecules to enter tumor cells, causing changes in tumor cell osmotic pressure and structural damage; Granzyme can penetrate the target cell membrane into its cytoplasm through the tubular structure constructed by perforin, activate caspase10, trigger caspase cascade reaction, and induce apoptosis of the target cell.

② Death receptor pathway: FasL on the surface of T cells binds to Fas on the surface of tumor cells, inducing tumor cell apoptosis through intracellular signal transduction.

③ Secretion of cytokines: T cells can secrete tumor necrosis factor, which binds to corresponding receptors on the surface of target cells and initiates apoptosis of target cells; It can also secrete cytokines such as interferon - γ, attracting immune cells such as macrophages to engulf and kill tumor cells.

Adoptive immune cell therapy involves isolating immune active cells from tumor patients, amplifying and functionally identifying them in vitro, and then reintroducing them back to the patient, in order to directly kill the tumor or stimulate the body's immune response to kill tumor cells.

At present, adoptive cell therapy includes CAR-T, TCR-T, NK cells, and TILs, as well as LAK therapy, DC therapy, CIK therapy, and DC-CIK therapy.

Therapy Contrast
NK therapy Natural Killer Cells, which do not rely on antibodies, have natural killing activity and help improve the body's immune environment

LAK therapy

Lymphokine Activated Killer Cells are induced by lymphokines and have broad-spectrum anti-tumor effects

DC therapy

Dendritic cells can activate the natural anti-tumor system in the human body, with stronger antigen presentation

CIK therapy

Cytokine Induced Killer Cells are mainly composed of NKT cells and are commonly used in advanced cancer patients

TIL therapy

Tumor infiltrating lymphocytes have stronger tumor specificity and shorter lasting cell activity

DC-CIK therapy

Cytokine induced killer cells mixed with dendritic cells, Hjt · eK Cytokine induced, have stronger killing power in mixed culture and are often combined with other treatment methods such as chemotherapy. They are suitable for the treatment of advanced tumors

CAR-T therapy

Lymphokine Activated Killer Cells do not require antigen presentation, can accurately locate tumor targets, and have strong persistence

TCR-T therapy

T-Cell Receptor chimeric T-cells can recognize and process presented antigens, and have a wide range of applications

The efficacy of TIL therapy in solid tumors

Patient baseline Indication Therapy Treatment Company

ORR%1

End of line treatment

 

 

Melanoma (NCT02360579 queue 2+queue 4)

TIL

Lifileucel

lovance

31% (2022ASco)

Non small cell lung cancer (NCT04614103)

TIL

LN-145

lovance

21.4%(2021.6.29)

Cervical cancer (NCT03108495 team has 4 unregistered cases)

TIL

LN-145

lovance

44%(N=27)

Frontline treatment

 

 

Melanoma (NCT03645928TIL+PD1 column 1A)

TIL+PD1

Lifileucel+pembrolizumab

lovance

60%(2021.9.22)

Non small cell lung cancer (NCT03645928 queue 2A)

TIL+PD1

Lifileucel+pembrolizumab

lovance

38.9%

Cervical cancer (NCT03H) 8495 queue 3

TIL+PD1

Lifileucel+pembrolizumab

lovance

57.1%(N=14)(2021.9.22)

 

Patient recruitment

If you meet the following basic requirements, you may be eligible to participate in this clinical study:

1. Age ≥ 18 years old, ≤ 75 years old, gender not limited;

2. Solid tumors such as AJCC (V8) stage III or IV malignant melanoma, non-small cell lung cancer, cervical cancer, head and neck squamous cell carcinoma that have failed standard treatment, cannot tolerate standard treatment, or have no standard treatment (diagnosed histologically); The patient has residual lesions that can be used for surgical resection (>1.5cm3) or biopsy and measurement after resection, for TIL collection and efficacy evaluation;

3. The first TIL treatment should be separated by at least 2 weeks from the end of the previous chemotherapy, radiotherapy, targeted therapy, biological therapy, or immunotherapy;
For detailed inquiries, please call: Teacher Liu | 17695804323