Kelly L. Lancaster

ORCID: 0009-0009-4750-199X
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About
Contact & Profiles
Research Areas
  • interferon and immune responses
  • Neuroblastoma Research and Treatments
  • Radiopharmaceutical Chemistry and Applications
  • Ubiquitin and proteasome pathways
  • Chemical Synthesis and Analysis
  • Monoclonal and Polyclonal Antibodies Research
  • HER2/EGFR in Cancer Research
  • Innovative Microfluidic and Catalytic Techniques Innovation
  • Virus-based gene therapy research
  • Immune Response and Inflammation
  • bioluminescence and chemiluminescence research
  • Biosimilars and Bioanalytical Methods
  • Peptidase Inhibition and Analysis
  • Advanced Biosensing Techniques and Applications
  • Cancer therapeutics and mechanisms
  • CAR-T cell therapy research
  • Cancer Research and Treatments
  • Computational Drug Discovery Methods
  • Synthesis and biological activity

Mersana Therapeutics (United States)
2021-2025

Abstract Activating interferon responses with STING agonists (STINGa) is a current cancer immunotherapy strategy, and therapeutic modalities that enable tumor-targeted delivery via systemic administration could be beneficial. Here we demonstrate tumor cell-directed agonist antibody-drug-conjugates (STINGa ADCs) activate in cells myeloid induce anti-tumor innate immune vitro, vivo (in female mice), ex models. We show the STINGa ADCs are internalized into by Fcγ-receptor-I antigen-dependent...

10.1038/s41467-024-49932-4 article EN cc-by Nature Communications 2024-07-11

While STING agonists have proven to be effective preclinically as anti-tumor agents, these promising results yet translated in the clinic. A agonist antibody–drug conjugate (ADC) could overcome current limitations by improving tumor accessibility, allowing for systemic administration well tumor-localized activation of greater activity and better tolerability. In line with this effort, a ADC platform was identified through systematic optimization payload, linker, scaffold based on multiple...

10.1021/acs.jmedchem.3c00907 article EN cc-by-nc-nd Journal of Medicinal Chemistry 2023-07-24

Abstract Purpose: Targeted tumor delivery may be required to potentiate the clinical benefit of innate immune modulators. The objective study was apply an antibody-drug conjugate approach STING agonism and develop a candidate. Methods: XMT-2056, HER2-directed STING-agonist (ADC), designed, built, tested in pharmacology toxicology studies. ADC compared benchmark intravenously administered agonist. Results: XMT-2056 achieved tumor-targeted agonist upon systemic administration mice induced...

10.1158/1078-0432.ccr-24-2449 article EN cc-by-nc-nd Clinical Cancer Research 2025-03-03

Abstract We present here a novel therapeutic agent, XMT-2056, that results in robust anti-tumor activity mediated by an immune response through targeted delivery of STING agonist to the tumor microenvironment. By leveraging antibody-drug conjugate (ADC) strategy, systemic administration with tumor-targeted can be achieved, potentially overcoming limitations either intratumoral or intravenous administrations unconjugated, small molecule agonists. XMT-2056 was generated conjugation...

10.1158/1538-7445.am2022-3503 article EN Cancer Research 2022-06-15

<p>Figure S5. A. PK profile of XMT-2056 in non-tumor bearing CB.17 SCID mice as a function total antibody (Total Ab) and conjugated drug concentrations plasma after single intravenous administration. Each line represents an individual animal (n=4). B. cynomolgus monkey during Q3W repeat-dose administration indicated by the black arrowheads. 1 male female were dosed; each data from one animal.</p>

10.1158/1078-0432.28911068 preprint EN 2025-05-01

<p>Figure S7. A. CB.17 SCID mice bearing subcutaneous JIMT-1 xenograft tumors were administered 3 weekly doses of XMT-2056, a combination non-binding control ADC and pertuzumab, or XMT-2056 pertuzumab. B. SNU-5 single dose ADC, ADCs intravenously while pertuzumab was intraperitoneally. Each point represents the mean tumor volume SEM (n=10).</p>

10.1158/1078-0432.28911062 preprint EN 2025-05-01

<p>Figure S8. A, B. BALB/c immune competent mice bearing syngeneic EMT-6-rHER2 tumors were treated with XMT-2056 surrogate ADC, anti-mouse PD-1 (Clone RPM1-14), non-binding control ADC in combination PD-1, or PD-1. The ADCs administered once while the mouse anti-PD-1 was twice weekly for 2 weeks as indicated by red triangles. A. Tumor volumes of individual mice, number complete responders (CR) indicated. Percent change body weight (BW). Each point represents mean BW and SEM (n=10).</p>

10.1158/1078-0432.28911059 preprint EN 2025-05-01

<p>Figure S2. A. STING mediated IRF3 activity of THP1 reporter cells expressing the indicated human STING1 haplotypes or knockout (KO) after treatment with agonist at doses. Each point represents mean and SD (n=2). B. Cytokine induction as measured by a multiplex Luminex assay from supernatants fresh white blood treated for 6 (IFN-β) 24 (CXCL10, IL-6, TNF-α) hours concentrations agonist. Bars represent value n=2 data points shown symbols. C. Structure HER2 extracellular domain showing...

10.1158/1078-0432.28911080 preprint EN 2025-05-01

<p>Figure S4. A. HER2 expression by IHC in SKOV3 xenograft tumors; scale bar, 20 µm. B. Percent changes body weights of tumor-bearing CB.17 SCID mice administered a single dose (black arrowhead) XMT-2056, non-binding control ADC, HT19, or STING agonist payload, 3 doses (orange the diABZI agonist. Each point represents mean change weight and SEM (n=10). C. Normalized counts for mouse mRNA human individual tumor cytokine/chemokines xenografts harvested 12 hours after treatment. SD (n=2)....

10.1158/1078-0432.28911071 preprint EN 2025-05-01

<p>Figure S3. A. Cancer cell death induced by XMT-2056, HT19 antibody, or non-binding control ADC, shown as percent viable SKBR3-NR (left) MDA-MB-175-VII-NR (right) cells in PBMC co-cultures (84 hr time point). Each point represents mean and SD (n=3). B. Cytokine induction HT19, ADC measured supernatants of (top) (bottom) (24 C. STING agonist payload monocultures MDA-MB-231-NR (n=3).</p>

10.1158/1078-0432.28911077 preprint EN 2025-05-01

<div>AbstractPurpose:<p>Targeted tumor delivery may be required to potentiate the clinical benefit of innate immune modulators. The objective study was apply an antibody–drug conjugate (ADC) approach STING agonism and develop a candidate.</p>Experimental Design:<p>XMT-2056, HER2-directed agonist ADC, designed, synthesized, tested in pharmacology toxicology studies. ADC compared with benchmark intravenously administered agonist.</p>Results:<p>XMT-2056...

10.1158/1078-0432.c.7797440 preprint EN 2025-05-01

Abstract Key defining attributes of an antibody–drug conjugate (ADC) include the choice targeting antibody, linker, payload, and drug-to-antibody ratio (DAR). Historically, most ADC platforms have used same DAR for all targets, regardless target characteristics. However, recent studies modeling suggest that optimal can depend on expression level intratumoral heterogeneity, internalization trafficking, characteristics linker payload. An platform enables optimization could improve success rate...

10.1158/1535-7163.mct-23-0262 article EN Molecular Cancer Therapeutics 2023-09-29
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