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Scientific Technology Centers

Driving Discovery
 
 
BKI scientist

Laboratory and clinical researchers at the Bloomberg~Kimmel Institute for Cancer Immunotherapy have access to state-of-the-art facilities and services designed specifically to support basic immunotherapy research.

Flow Cytometry and Human Immunology Technology Center

The Flow Cytometry and Human Immunology Technology Center is developing high-dimensional (up to 50 color) flow cytometry and high directional sorting capabilities to define more specifically the multiple subsets of immune cells in both the tumor microenvironment and peripheral blood. This center will employ the most recent instrumentation innovations, including high-dimension instruments in beta-testing. Additionally, novel T cell assays, termed MANAFEST and TIAAFEST, will be used together with new bioinformatics platforms to assess the vast repertoire of tumor-specific T cells.

Training, data analysis and consultation services are available.

Resource director: Drew Pardoll, M.D., Ph.D.

Tumor Microenvironment (TME) Technology Center

Studies of the tumor microenvironment (TME) — the surrounding cellular environment of the tumor — are responsible for the successful development of fundamental paradigms for cancer immunotherapy. Difficult questions remain, including why some patients respond to immune checkpoint blockades while others don’t. Solving these questions is pivotal to improving how well these drugs work in certain patients.

The Tumor Microenvironment Technology Center employs advanced technology to conduct the basic scientific research that supports the many investigations made by our scientific programs.

Resource director: Suzanne Topalian, M.D.

Primary Goals

Characterize the heterogeneity of the TME and correlate the evolution of anti-tumor immune responses with the clinical behavior of metastatic lesions in response to immunotherapy

We hypothesize that dynamic and interacting immunological factors influence the growth, spread or regression of tumors, especially during treatment with immune checkpoint blocking drugs.

The TME Technology Center will study tumor-host interactions in chronologically and anatomically diverse tumor lesions using novel multiplex immunohistochemistry (IHC) techniques and molecular expression assays. The research will draw correlations between immunological signatures and tumor regression or progression. It will also provide insights into what causes the partial and “mixed” tumor regressions frequently observed in patients receiving anti-PD-1/PD-L1, and will reveal new targets for therapies aimed to convert partially-responding tumors to complete responders.

Compare the TME in cancers from immunosuppressed vs. immunocompetent individuals

Lung cancers, melanomas and other skin cancers arise more frequently in immunosuppressed individuals, such as transplant recipients or HIV-positive patients. This suggests that disturbing the balance in the immune system can cause cancer to form. Such individuals typically have been excluded from immunotherapy trials, since it is believed that they are not capable of responding to immune-based drugs.

The TME Technology Center will expand the Institute’s understanding of the immune evasion and selection model of cancer development in immunosuppressed patients, and in doing so, determine how to best incorporate immunomodulatory therapeutics in treatment plans. These studies may increase our knowledge of innate immune mechanisms governing anti-tumor immunity, including novel immune regulatory molecules that could be targeted clinically.

Analyze the effects of signaling pathway inhibitor therapies on anti-tumor immunity

Over 50% of melanomas share common mutations in the MAPK signaling pathway, predominantly BRAF V600E, and several new small molecule drugs blocking mutant BRAF or MEK, a downstream signaling molecule, have been approved recently for patients with advanced melanoma whose tumors express mutant BRAF. This experience has established a paradigm for oncogene-targeted small molecule therapies in various cancer types: induction of dramatic but short-lived tumor regressions, with outgrowth of resistant tumors exhibiting new genetic alterations. Kinase inhibitors have also been shown to have various effects on anti-tumor immune responses.

The TME Technology Center will develop molecularly guided, synergistic treatment regimens combining small molecule inhibitors with immune-based treatments. This will be done using serial biopsies of metastatic lesions in patients with melanoma or lung cancer receiving tyrosine kinase inhibitors, and with in-depth analysis and characterization of dynamic changes in the tumor immune microenvironment.

Drug Development Technology Center

The Drug Development Technology Center, which is part of Johns Hopkins Drug Discovery, plays a critical role in helping Bloomberg~Kimmel Institute scientists translate their basic science discoveries into small molecule therapeutics by providing its core expertise in the following areas:

  • Medicinal Chemistry
  • Assay Development and Screening
  • Drug Metabolism and Pharmacokinetics
  • Animal Pharmacology/Toxicology​

One of the major challenges encountered by academic institutions aiming to develop new therapeutics has been the lack of a truly dedicated drug discovery/development unit. The Drug Development Technology Center is staffed with seasoned drug discovery and development experts with extensive industry experience in the pharmaceutical sector. The center was designed to complement the strength of academic research by bridging a gap between basic science and therapeutic application.

Resource director: Barbara Slusher, Ph.D., M.A.S.

Specific services include:

Medicinal Chemistry

  • Small molecule chemical synthesis
  • Structure activity relationship studies
  • Hit-to-lead and lead optimization
  • Prodrug design

Assay Development and Screening

  • Protein expression/purification
  • Establishment of enzyme, receptor, transporter biochemical, cell-based, and phenotypic screening assays using calcium imaging, fluorescence, absorbance, LC-MS, and radioactivity detection
  • Screening libraries available, including FDA library, LOPAC, CNS Diverset (ChemBridge), and IOCB Proprietary Drug Library

Drug Metabolism and Pharmacokinetics

IN VITRO PHARMACOKINETICS
  • Plasma and metabolic stability
  • Metabolite Identification  
  • Intestinal Permeability (Caco-2, MDCK, PAMPA)
  • P-gp Substrate Assessment
  • Plasma and brain protein binding
IN VIVO PHARMACOKINETICS
  • Pharmacokinetics and tissue distribution (mice, rats, monkeys, pigs) following acute and chronic dosing, including PO, IV, IP, SC and intranasal (IN) routes
  • Bioanalysis in biological matrices
  • Dose Vehicle Assessment
  • Pre-formulation Assessment
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