LANDscape MApping of Epitopes and T Cell Receptors for Selected Cancers (LANDMARC)

This is a correlative research project aimed at characterizing the T cell mediated immune responses to hepatocellular carcinoma (HCC), as well as Epstein-Barr virus (EBV)- and human papillomavirus (HPV)-related cancers. This study will enroll approximately 105 patients over 48 months. Of these 105 patients, 30 are EBV-related cancer, 45 are HPV-related cancer, and 30 are HCC. Patients will have blood samples collected one time to identify cancer specific T cells and T cell receptors in their blood. They will also have tissue samples collected one time to study the different types of immune cells, especially the T cells and their receptors.

The 105 patients enrolled in this study will be compared to retrospective samples (N=210; 30 from EBV-related cancer cohort, 180 from HPV-related cancer cohort).

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor

Detailed Description

The cloning of genes encoding the T cell receptor (TCR), the identification of tumor-associated antigens and the subsequent characterization of the first HLA-restricted T cell-defined antigenic epitope, were key findings illustrating direct recognition of cancer cells by T cells. These discoveries provided a mechanistic foundation for ensuing work examining the dynamic nature of lymphocyte-dependent recognition and elimination of neoplastic cells. Furthermore, preclinical and clinical investigations illustrate an important role for T cell mediated anti-tumor immunity in human disease, and have characterized the complexity of cancer-associated immune responses that are not always sufficient for tumor elimination. Importantly however, therapeutic targeting of the immune system has demonstrated the power of immunomodulatory drugs for the restoration of anti-tumor immune responses for cancer treatment.

Presence of lymphocytes in a variety of human cancers is well documented, and T cells isolated from tumors that recognize cancer antigens can be harnessed for effective treatment. T cells isolated from patient tumors can be ex vivo expanded, and reinfused back into patients in a regime of cellular therapy termed adoptive cell transfer (ACT). This ACT therapy can be further directed to specific tumor antigens with the genetic manipulation of T cells to express TCR recognizing known p-HLA epitopes with dominant expression on cancer cells. However, the peptide-HLA (p-HLA) epitope landscape of tumor associated antigens, and their cognate TCR are not well described, and those which have been described are primarily limited to the class I HLA-A*02:01 allele dominant only in European-Caucasian populations. The purpose of this study is to further document the cancer epitope landscape and provide a comprehensive characterization of TCR specificities in a range of malignancies, for a wide variety of class I and class II HLA alleles. In addition, we aim to elucidate not only TCR repertoires important for anti-tumor immunity, but further clarify the role antigen presenting cells play in shaping these T cell repertoires.

The objectives involve the identification of cancer-associated/specific antigen p-HLA epitopes and their cognate TCR, and the subsequent structural and functional characterization these TCR. To meet this objective, immune cells of T, B and myeloid lineage will be analyzed. Phenotypic characterization of these cell subsets will be performed using standard immunological procedures such as immunofluorescence, immunohistochemistry, ELISA, ELISpot, qRT-PCR, analytic cytometry, CyTOF (cytometry time of flight), and in vitro stimulation. To relate immune responses to cancer cell intrinsic biology, RNA and DNA will be sequenced to identify cancer cell transcriptome and mutations, as well as T cell receptor unique sequences. Results from all laboratory analysis will be combined with relevant clinical data. Any confirmation of diagnosis, tissue types and other clinical data will be provided as available from the pathologists of the relevant disease site at UHN.

An incomplete understanding of T cell responses to cancer impedes the development of more effective immunotherapeutics. Discovery using tumor specimens from cancer patients will clarify how the complexity of the tumor environment shapes T cell specificity to induce effective immune responses and facilitate our development of better immune modulating therapeutics.

• Study Type: Observational
• Enrollment (Estimated): 105

Contacts and Locations

• Study Contact: Name: Kathy Han, MD; Phone Number: 6522 416-946-4501; Email: tip@uhn.ca
• Study Contact Backup: Name: Kendra Ross; Phone Number: 7754 416-946-4501; Email: kendra.ross@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Kathy Han, MD; Phone Number: 6522 416-946-4501; Email: tip@uhn.ca
      • Contact: Kendra Ross; Phone Number: 7754 416-946-4501; Email: kendra.ross@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Solid tumor patients, including patients with hepatocellular carcinoma (HCC) patients and Epstein-Barr virus (EBV)- human papillomaviruses (HPV)-related cancers.

Description

Inclusion Criteria:

1. Patients with a histological or cytological diagnosis of:

   1. EBV-related malignancies (e.g. nasopharyngeal cancer)

   2. HPV-related malignancies, including squamous cell carcinoma of the head and neck, cervix, vulva or anal canal. HPV positivity is required for squamous cell cancers of the head and neck.; p16 positivity as a surrogate for HPV testing is acceptable. HPV positivity is not required for cervix, vulva or anal canal cancer.

      • For cancers of the anal canal, late stage distant metastatic tumor tissue is preferred. However, early stage primary site tissue is acceptable, if the tissue can be procured without contamination by intestinal microbiota.
   3. For HCC, only patients who have above UHN institutional upper limit of normal levels of alpha-fetoprotein (AFP) in serum will be eligible. The diagnosis of HCC should be made based on standard of care with or without tumor tissue confirmation.
2. Patients must be ≥ 18 years old.
3. Patients must have provided voluntary written informed consent.

Exclusion Criteria:

1. Any condition that, in the opinion of the Investigator, would interfere with patient safety, or evaluation of the collected specimens and interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
EBV-related cancer cohort; up to N=30
HPV-related cancer cohort; up to N=45
HCC cohort; up to N=30

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identifying the p-HLA epitopes across diverse HLA alleles	To identify the p-HLA epitopes, we will examine a variety of clinically relevant tumor antigens, including alpha feto-protein (AFP) and carcinoembryonic antigen (CEA) in HCC, and canonical and cryptic protein antigens specific to the EBV-sequence and HPV-sequence open reading frames (ORFs).	63 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterizing tumor-antigen specific TCR repertoire diversity across diverse HLA alleles, and further provide a comprehensive functional analysis that identifies immunodominant epitopes important for tumor control	To characterize, we will map the landscape of anti-tumor TCR repertoire diversity, and characterize the functional heterogeneity of clonotypic T cell responses for the cancer-type specific antigens. Where tumor tissue is available, comprehensive comparative analysis of immune populations in the peripheral blood will accompany those analyses of tumor tissue. Peripheral blood samples will be used for the three specific endpoints, including; 1) assessment of the functionality, composition, relative percentage, and absolute number of various immune cell populations, 2) quantitation of soluble factors influencing immune cell function, and 3) a comprehensive phenotypic and functional characterization of tumor specific T cells in the periphery.	63 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Kathy Han, MD, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; solid tumor; Epstein-Barr Virus related cancer; Human Papilloma Virus related cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: LANDMARC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: There may be data sharing in the future for potential collaborations with external researchers within the scope of the study objectives.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No