Importance of T cells in Cancer Immunotherapy

Cancer cells have developed strategies to escape and suppress the immune system which results in a failure to initiate and maintain adequate anti-tumor immunity, and consequently facilitates tumor survival and progression. Strategies include tumor antigens being only weakly immunogenic. Tumors may down regulate or modulate the expression of antigens, thus evading immune-cell detection. In addition, tumors can suppress the immune response through the synthesis of various immune suppressants that have roles in maintaining self-tolerance, or that inhibit effector immune cell function. Tumor immune suppression affects all branches of the immune system and can result in tumor escape from the immune system.

T cells (also known as T lymphocytes) are found widely distributed within tissues and the tumor environment. They play a central role in cell-mediated immunity and can mediate long-lived, antigen specific, effector and immune memory responses. T cells express T cell receptors (TCR) that confers antigenic specificity on the T cell, by recognizing an antigen ligand comprising a short contiguous amino acid sequence of a protein that is presented on the tumor cell.

Tumor cells might insufficiently stimulate antigen-presenting cells in tumor microenvironment resulting in inadequate expression of MHC class I- and II-peptide molecules, co-stimulatory molecules and cytokine production. The antigen-presenting cells therefore cannot fully engage with the TCR on the T cells and thereby leading to suboptimal T-cell activation, proliferation and expansion, resulting in T cells inability to kill tumors.

Targeting the T cell-tumor interactions and blocking their interaction to activate T cells has led to the development and approval of groundbreaking cancer immunotherapies such as Keytruda and Opdivo (anti-PD1) and Tecentriq (anti-PDL1)

What are the advantages of HLA-matched T cell and Tumor Cell Lines?

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HIGHER SPECIFICITY

Higher specificity results in exquisite sensitivity between the TILs and tumors, resulting in an increased ability to detect the impact factors within the tumor microenvironment that could be masked by allogeneic responses.

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WELL CHARACTERIZED

Highly characterized tumors (e.g. Braf mutations and STR profiles are known). Huge panel from which one can assess the impact of potential drugs.
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ESTABLISHED DATA WITH APPROVED IMMUNE MODULATORS

Established data with anti-PD1 and anti-PD-L1 drug candidates – good for comparative studies.
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REPEAT STUDIES ACROSS ASSAY FORMATS

A standardized and reproducible system which with one can assess immune responses across various platforms.

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BROAD SPECTRUM APPLICATIONS IN CANCER

Apply readouts into other tumor types or indications

Specificity

These cell lines provide greater specificity than allogeneic T cells and tumors

Characterized

Our cell lines are genomically characterized and provide for valuable assay use

Reproducible

Reproduce results beyond one experiment and across multiple 2D, 3D and in vivo assay formats

Validation

Confirm and/or confirm your internal results based on tumor lysis and cytokine readouts

CTL 007 and WC 007 (colon cancer)

Background

CTL 007 and WC 007 represent a unique, autologous and well characterized colon cancer cell lines that were developed at the Wistar Institute. The patient (007) had primary CRC, Dukes’ stage B2, and currently has no clinical evidence of disease 6 years after resection of the primary tumor.

 

Internal characterization

We have further characterized WC 007 for expression of key markers. These include but not limited to:

We have characterized additional genomic and cell surface makers and work with clients in determining the expression of their drug target. Please contact us to learn more.

 

Assays conducted to date

 

  • Comparative studies using Keytruda (anti-PD-1) and Tecentriq (anti-PD-L1) candidates to measure tumor lysis)
  • Comparative studies using Yervoy (anti-CTLA4)
  • Effect of drug candidate(s) on CTL 007 migration in 3D co-culture with WC 007
  • Immunosuppressive studies using allogeneic Tregs and Macrophages on CTL 007 inhibition of WC 007 lysis

CTL 020 and WC 020 (colon cancer)

Background

CTL 020 and WC 020 represent a unique, autologous and well characterized colon cancer cell lines that were developed at the Wistar Institute. The patient (020) had primary CRC, Dukes’ stage B2, and currently has no clinical evidence of disease 6 years after resection of the primary tumor.

 

Internal characterization

We have further characterized WC 020 for expression of key markers. These include but not limited to:

We have characterized additional genomic and cell surface makers and work with clients in determining the expression of their drug target. Please contact us to learn more.

 

Assays conducted to date

  • Comparative studies using Keytruda (anti-PD-1) and Tecentriq (anti-PD-L1) candidates to measure tumor lysis.
  • Comparative studies using Yervoy (anti-CTLA4).
  • Effect of drug candidate(s) on CTL 020 migration in 3D co-culture with tumor 020.
  • Immunosuppressive studies using allogeneic Tregs and Macrophages on CTL 020 inhibition of tumor 020 lysis.

CTL 002 and Tumor 002 (colon cancer)

Background

CTL 020 and WC 020 represent a unique, autologous and well characterized colon cancer cell lines that were developed at the Wistar Institute. The patient (020) had primary CRC, Dukes’ stage B2, and currently has no clinical evidence of disease 6 years after resection of the primary tumor.

 

Internal characterization

We have further characterized WC 020 for expression of key markers. These include but not limited to:

    • CTL 020      – CD4, TIM-3, CD25, GITR, OX-40,4-1BB,
    • WC 020       – 4-1BBL, HVEM, OX-40L, CD155, CD112,CD80

We have characterized additional genomic and cell surface makers and work with clients in determining the expression of their drug target. Please contact us to learn more.

 

Assays conducted to date

  • Comparative studies using Keytruda (anti-PD-1) and Tecentriq (anti-PD-L1) candidates to measure tumor lysis.
  • Comparative studies using Yervoy (anti-CTLA4).
  • Effect of drug candidate(s) on CTL 020 migration in 3D co-culture with tumor 020.
  • Immunosuppressive studies using allogeneic Tregs and Macrophages on CTL 020 inhibition of tumor 020 lysis.

For additional information and data related to these cell lines, please Contact us to learn more

This is a PD-L1 sensitive tumor line

TIM-3, PD-1, CD25, CD80, HVEM, GITR, CD73, PD-L2, OX-40L, CD155, CD112, CD44, CD49a (α1 integrin), CD49b (α2 integrin), CD29 (β1 integrin), CD95 (FAS) CD54 (ICAM-1), CD11a (LFA-1a)

CTL and Tumor 001 was derived from a colon cancer patient. This HLA-matched pairing is PD-L1 sensitive.

Tumor 001

PD-L1, HVEM, OX-40L, CD155, CD112, CD44,
CD49b(α2 integrin), CD29(β1 integrin), CD95 (FAS)

Chemokines and Chemokine Receptors

CCR2,CCR3, CCL15,CCL2,CCL3,CCL4,CXCL11, CCL19,CCL21, CCL25, and CXCL9

Example studies:

  • Cytotoxity (CTL) studies
  • Immunosuppression assays to evaluate the role of Tregs and Tumro Associated Macrophages (TAMs) on CTL proliferation and apoptosis of matched tumor
  • Blocking and binding studies of known cell surface targets

 

This is a PD-1 sensitive tumor line

CTL and Tumor 002 derived from a female colon cancer patient at time of surgery. This HLA-matched cell pairing is PD-1 sensitive.

PD-1, TIGIT, OX-40, 4-1BB, CD80, CD44, CD95 CD29(β1 integrin), CD3, TCR α/β, CD95 (FAS), CD54 (ICAM-1), CD11a (LFA-1a)

Tumor 002

PD-L1, HVEM, OX-40L, CD155, CD112, CD44 CD49a (α1 integrin), CD49b (α2 integrin), CD29 (β1 integrin), CD95 (FAS)

Chemokines and Chemokine Receptors

CCR2,CCR3, CCL15,CCL2,CCL3,CCL4,CXCL11, CCL19,CCL21, CCL25, and CXCL9

Example studies:

  • Cytotoxity (CTL) studies
  • Immunosuppression assays to evaluate the role of Tregs and Tumro Associated Macrophages (TAMs) on CTL proliferation and apoptosis of matched tumor
  • Chemokine blocking studies of SDF1α and CXCR4
  • Blocking and binding studies of known cell surface targets

 

This is a PD-1 sensitive tumor line

CTL and Tumor 003 derived from a melanoma male Caucasian patient. This HLA-matched cell pairing is PD-1 and PD-L1 sensitive.

TIM-3, PD-1, 4-1BB, ICOS, CD8, CD25, CD44
CD95 (FAS),CD80(B7-1), CD29(β1 integrin), CD49b (α2 integrin), CD54 (ICAM-1), CD11a (LFA-1A)

Tumor 003

PD-L1, CD44, ICOSL, 4-1BBL, PD-L2, CD112, HVEM, CD49a (α1 integrin), CD49b (α2 integrin), CD29 (β1 integrin), CD95 (FAS)

Chemokines and Chemokine Receptors

CCR7,CCR9, CXCR3,CXCR1, CCL21,CCL25, CXCL12,CXCL19 and CXCL9

Example studies:

  • Cytotoxity (CTL) studies
  • Immunosuppression assays to evaluate the role of Tumro Associated Macrophages (TAMs) on CTL proliferation and apoptosis of matched tumor
  • Chemokine blocking studies of SDF1α and CXCR4 and affects on CTL migration
  • Blocking and binding studies of known cell surface targets