Immunotherapy

Is a type of treatment that harnesses the power of our own immune system to treat cancer. In the last decade, cancer immunotherapy has become a foundation for cancer treatment approved for more than a dozen types of cancer, but it comes with its own challenge as not all cancer immunotherapies work for all patients.

Immune checkpoint targets

Immune checkpoint inhibitors (ICB), the most common type of immunotherapy targeting PD(L)-1 and CTLA-4 typically elicits durable response only in a subset of patients (20-40%) with solid tumors. The majority of patients either do not respond to immunotherapy, acquire resistance, or are limited by treatment-related immune toxicities. Predicting response to ICB remains a challenge and improving our understanding of response biology and mechanism of resistance has become increasingly important. Due to the complex relationship between the dynamic nature of the host immune system and tumor biology, combined efforts and tools are required to accelerate research and design better treatment options essential to expand the benefits of immunotherapy for non-responding patients beyond the success of current ICB.

Accelerating progress in cancer immunotherapy

Predictive biomarkers remain a rapidly emerging area of research in immunotherapy. In recent years, the development of minimally invasive and robust liquid biopsy-based biomarkers has become urgently needed. Several liquid biopsy targets including ctDNA and CTC are currently under investigation as a promising marker for treatment response. While proteins represent an important liquid biopsy target with the ability to characterize the activity of a patient’s immune system and their tumor, assessment and the utility of circulating proteins for immunotherapy is largely unexplored due to the lack of technological advances.

Olink’s solutions for protein biomarker discovery (Olink Explore 1536 and Olink Target 96 panels) are being increasingly used in immunotherapy studies across different tumor types and different immunotherapy treatment strategies and settings. These include:

Objectives:

• Predict and monitor treatment response, patient stratification
• Tumor biology insight, mechanism of immune modulation, phenotype changes, transformation cold to hot tumors
• Clarify the interconnected roles of tumor genomics, transcriptomics and proteomics in predicting response to immunotherapy
• Treatment sensitivity and mechanism of immune resistance, design of strategies to optimize response rates and identify novel targetable pathways
• Assess the longitudinal biomarker changes between early timepoints (baseline to treatment) and later timepoints (baseline to disease progression) to identify key markers associated with the transition from a drug-sensitive to drug-resistant state
• Explore the association between baseline circulating immune proteins and patient outcome (OS and PFS)
• Predict onset and mechanism of treatment associated toxicity, monitoring CRS and neurotoxicity
• Predict recurrence and on-treatment progression in adjuvant settings

Cancer types:
Melanoma, NSCLC, Prostate, Pancreatic, Breast, Gastroesophageal, Gastric, Colorectal, Urothelial bladder, Hepatocellular, Lymphoma

Treatment types:
ICB, T cells (CAR-T cells, NK cells), Adenovirus, Cancer vaccines, Bi-specific Ab and PD-1 combinations: Chemo, SBRT, VEGF/R, TKI, Cytokines

Recommended products for immunotherapy applications

• Olink Explore 1536 (high throughput screening of ~1500 proteins with NGS readout)
• Olink Target 96 panels:
  • Olink Target 96 Immuno-oncology
  • Olink Target 96 Inflammation
  • Olink Target 96 Oncology II
  • Olink Target 96 Oncology III
  • Olink Target 96 Immune Response
• Olink Target 48 Cytokine

Collaborative research initiatives

CIMAC-CIDC

The Cancer Immune Monitoring and Analysis Centers-Cancer Immunologic Data Commons (CIMAC-CIDC) Network was launched in 2017 through the Cancer Moonshot^SM initiative supported by the NCI and collaborates with another Cancer Moonshot project, the Partnership for Accelerating Cancer Therapies (PACT). Olink has been chosen as the core assay for profiling of cytokines, chemokines, and growth factors within this project, as reported in a recent article from CIMAC-CIDC/PACT:

Chen et al (2021) Clin. Cancer Res, DOI: 10.1158/1078-0432.CCR-20-3241 – article link

You can also read more about this important initiative for cancer immunotherapy research at the CIMAC-CIDC website

Maastricht University Medical Center

An exploratory prospective study, performed in collaboration with Maastricht University Medical Center, investigated circulating biomarkers of immunogenic cell death (ICD) after radiotherapy and chemotherapy in stage III NSCLC and identified important changes in immune protein profile. The overarching goal in ongoing follow-up prospective study is to improve the therapeutic efficacy of immunotherapy in stage III NSCLC patients treated with concurrent chemotherapy and photon or proton radiotherapy and adjuvant durvalumab (anti-PD-L1). Some of this work will be presented at AACR 2021, in a presentation entitled, “Biomarkers in Radiotherapy” that will be held in the session “Advances in Diagnostics and Therapeutics Session Proton Therapy and FLASH Irradiation” on Monday, April 12, 2021.

“To exploit immunotherapy for cancer optimally, biomarkers are essential for, they will lead to a personalized selection of the best treatment during the course of the disease. Blood biomarkers are ideal in this respect as they allow repeated sampling and avoid sampling heterogeneity within the tumor and between tumor locations in the same patient as is the case with tumor biopsies.”

Dr. Dirk de Ruysscher, Professor of Respiratory Oncology, Maastricht University Medical Center, Maastro Clinic, Netherlands

Babačić H,  Lehtiö J, Pico de Coaña Y, Pernemalm M and Eriksson H. In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma. (2020) Journal for ImmunoTherapy of Cancer, DOI: 10.1136/jitc-2019-000204
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Kasanen H, Hernberg M, Mäkelä S, Brück O, Juteau S, Kohtamäki L, Ilander M, Mustjoki S and Kreutzman A. Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients. (2020) Cancer Immunology, Immunotherapy, DOI: 10.1007/s00262-020-02497-9
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Pedersen JG, Madsen AT, Gammelgaard, KR, et. al.  Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors. (2020) Cancers, DOI: /10.3390/cancers12061414
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Taylor M, HugheRs A, Walton J, Coenen-Stass A, Magiera L, Mooney L, Bell S, Staniszewska A, Sandin L, Barry S, Watkins A, Carnealli L and Hardaker E. (2019) Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery. Journal for Immunotherapy of Cancer, DOI: 10.1186/s40425-019-0794-7

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Enblad G, Karlsson H, Gammelgård G, Wenthe J, Lövgren T, Amini M, Wikstrom K, Essand M, Savoldo B, Hallböök H, Höglund M, Dotti G, Brenner M, Hagberg H and Loskog A. (2018) A Phase I/IIa Trial Using CD19-Targeted ThirdGeneration CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-18-0426
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SEE ALL CURRENT OLINK PUBLICATIONS IN IMMUNOTHERAPY>

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