Therapeutic Intralesional Program

Overview

The Therapeutic Intralesional Program (TIP) is a multi-disciplinary team of clinicians and researchers working together to create infrastructure and a community of experts focused on direct-to-tumor therapies across multiple tumor types. A primary initiative is to create a portfolio of clinical trials relating to direct-to-tumor therapies in various settings (neoadjuvant, adjuvant, metastatic disease) including therapeutic approaches such as in situ vaccines, oncolytic viruses, immune adjuvants, and ablative therapies This trial system incorporates a robust correlative research infrastructure and interfaces with a variety of programs including imaging, bioengineering, and computational/systems biology. We incorporate two primary Mass General missions: excellence in clinical care and cutting-edge research.

What are Intralesional Therapies?

Intralesional therapies are any type of treatment in which the therapy (drug or intervention) is directly targeted to the tumor, instead of being delivered via the blood stream. This includes direct injection of drugs/viruses/vaccines into the tumor and also includes ablative therapies that directly target/kill the tumor such as radiation or cryoablation (“freezing the tumor”).

Advancing Care through Research and Clinical Trials

Direct-to-tumor therapies (vaccines, oncolytic viruses, immune adjuvants, ablative therapies) are a new area of growth, but a fragmented infrastructure and lack of integration across disciplines are obstacles for current programs. The Therapeutic Intralesional Program at the Mass General Cancer Center aims to leverage the broad-based expertise of one of the nation’s pre-eminent general hospitals to provide patients with access to cross-disciplinary trial opportunities by bringing together the clinical and research expertise of Mass General faculty from various disciplines, including: Dermatology, Engineering, GI, Imaging, Immunology, Inpatient Oncology, Interventional Radiology, Nursing, Outpatient Oncology, Pathology, Pharmacy, Radiation Oncology, Research, and Surgery.

The goals of the Therapeutic Intralesional Program are:

• Establish a multi-disciplinary team of experts and synergize resources for direct-to-tumor therapies in multiple tumor types and across various disciplines
• Develop a portfolio of clinical trials relating to direct-to-tumor therapies in various settings (neoadjuvant, adjuvant, metastatic disease)
• In situ vaccines, oncolytic viruses, immune adjuvants, radiation or ablative therapies alone or in combination with other systemic therapies, such as immunotherapy
• Create a built-in correlative research structure
• Incorporate two of Mass General’s primary missions:
• Excellence in clinical care
• Cutting-edge research

Our areas of focus include:

• Disease-specific team “champions” from areas including, Melanoma, Breast, GI, Head/Neck, Thoracic
• Infrastructure and resource integration
• Cross-disease trial opportunities
• A broad patient base including early disease (prevention trials) and late-stage disease (therapeutic trials)
• Neoadjuvant “window of opportunity” – trials in which the biology of responses can be interrogated
• We are strongly focused on improving the patient experience via robust support for outpatient access and referral management for physicians/providers
• Research Coordination / Research Management

Clinical Trials

View open clinical trials:

• Study of Core Needle Biopsy and Cryoablation of an Enlarging Tumor in Patients With Metastatic Lung Cancer and Metastatic Melanoma Receiving Post-progression Immune Checkpoint Inhibitor Therapy
• Topical Calcipotriene Treatment for Breast Cancer Immunoprevention
• Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)
• A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)
• rRp450-Phase I Trial in Liver Metastases and Primary Liver Tumors

 

Literature & Publications

• Mahvi DA, Liu R, Grinstaff MW, Colson YL, Raut CP. Local Cancer Recurrence: The Realities, Challenges, and Opportunities for New Therapies. CA Cancer J Clin. 2018 Nov;68(6):488-505.
• Ekladious I, Colson YL, Grinstaff MW. Polymer-drug conjugate therapeutics: advances, insights and prospects. Nat Rev Drug Discov. 2019 Apr;18(4):273-294.
• Mooradian M, Fintelmann F, Fadden R, et al. A phase II study of cryoablation (cryo) of an enlarging tumor in patients (pts) with advanced lung cancer or melanoma receiving post-progression immune checkpoint inhibition (ICI). J Clin Oncol. 2019 May. doi: 10.1200/JCO.2019.37.15_suppl.e14243. (view poster here)

Therapeutic benefits of tumor targeting, or tumor specific drug expression

• Dougan M, Ingram JR, Jeong HJ, Mosaheb MM, Bruck PT, Ali L, Pishesha N, Blomberg O, Tyler PM, Servos MM, Rashidian M, Nguyen QD, von Andrian UH, Ploegh HL, Dougan SK. Targeting cytokine therapy to the pancreatic tumor microenvironment using PD-L1 specific VHHs. Cancer Immunol Res. 2018.
• Ingram JR, Blomberg OS, Sockolosky JT, Ali L, Schmidt FI, Pishesha N, Espinosa C, Dougan SK, Garcia KC, Ploegh HL, Dougan M. Localized CD47 blockade enhances immunotherapy for murine melanoma. Proc Natl Acad Sci USA. 2017 Sep 19;114(38):10184-10189.

Review on tumor microenvironment targeting

• Dougan M, Dougan SK. Targeting Immunotherapy to the Tumor Microenvironment. J Cell Biochem. 2017 Oct;118(10):3049-3054.

Imaging the tumor immune microenvironment

• Rashidian M, Keliher EJ, Dougan M, Juras PK, Cavallari M, Wojtkiewicz GR, Jacobsen JT, Edens JG, Tas JMJ, Victora G, Weissleder R, Ploegh H. Use of 18F-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer. ACS Central Science. 1, 142–147 (2015).
• Rashidian M, Ingram JR, Dougan M, Dongre A, Whang KA, LeGall C, Cragnolini JJ, Bierie B, Gostissa M, Gorman J, Grotenbreg GM, Bhan A, Weinberg RA, Ploegh HL. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med. 2017 Aug 7;214(8):2243-2255.
• Ingram JR, Dougan M, Rashidian M, Knoll M, Keliher EJ, Garrett S, Garforth S, Blomberg OS, Espinosa C, Bhan A, Almo SC, Weissleder R, Lodish H, Dougan SK, Ploegh HL. PD-L1 is an activation-independent marker of brown adipocytes. Nat Commun. 2017 Sep 21;8(1):647.
• Ingram JR, Blomberg OS, Rashidian M, Ali L, Garforth S, Fedorov E, Fedorov AA, Bonanno JB, Le Gall C, Crowley S, Espinosa C, Biary T, Keliher EJ, Weissleder R, Almo SC, Dougan SK, Ploegh HL, Dougan M. Anti-CTLA-4 therapy requires an Fc domain for efficacy. Proc Natl Acad Sci USA. 2018.