2025-2026 MCW Radiation Oncology Annual Report - Flipbook - Page 23
2025-2026 Medical College of Wisconsin, Radia琀椀on Oncology Annual Report
Leukapheresis
Circulatin
g T cells
CRISPR-Cas9
Endogenous
TCR KO
T3 oligoclonal
TCRengineered
OSCC
Biopsy
T3 expansion
and release
testing
Prolif_Tox Lentiviral packaging
Single-cell T
and transduction
transcriptomics TCRs
Radiation
T3 product
infusion
Figure 11.
Schema for
the
REACTR
T3 Outcomes
Safety
Tumor infiltration
Systemic durability
6 weeks
72 hours
post-infusion post-infusion
Functional
immunophenotype
Effect on tumor
microenvironment
Figure 2. REACTR Concept. Tprolif_tox clonotypes will be engineered ex vivo and delivered post-radiation to
restore tumor-specific immunity after radiation.
While wai琀椀ng for the results of our bench research, we have more recently proposed two new trials building on the
backbone of DEHART and HyPR-HN: REACTR and INITIUM-HN. REACTR proposes injec琀椀on of T cells carrying the three
most common Tprolif_tox T-cell receptors a昀琀er the DEHART regimen to target subclinical distant metastases (Fig 2), while
INITIUM-HN will study immunologic changes in a novel combina琀椀on of immunotherapy and radia琀椀on for resectable HNC.
Both have been submi琀琀ed as R01 proposals to the NCI, with INITIUM-HN also having received preliminary no琀椀ce of
funding through the ROCKET program and Cancer Center. We will leverage serial single-cell biopsies from these trials to
see if these approaches could successfully overcome the impact of radia琀椀on on the tumor-immune microenvironment
and also understand how immunotherapy alters this unique cell popula琀椀on.
Finally, we are working to reduce poten琀椀al toxicity of hypofrac琀椀onated radia琀椀on for HNC by studying osteoradionecrosis
(ORN) in a mul琀椀-pronged approach. First, we have developed a novel mouse model of osteoradionecrosis resul琀椀ng from
the DEHART regimen. Second, we have laid the groundwork for a collabora琀椀on with Dr. Sarah Kerns and Dr. Behzooz
Alizadeh from the Netherlands, to understand gene琀椀c predictors predisposing pa琀椀ents to ORN using data from the
UMCG-HANS study. This has led to the development of an R01 proposal currently under review tes琀椀ng ways to reduce
ORN in the mouse model, evalua琀椀ng changes in osteoblasts from pa琀椀ents that developed ORN on our trials of
hypofrac琀椀onated radia琀椀on and u琀椀lizing the UMCG-HANS data to determine single nucleo琀椀de polymorphisms predic琀椀ve
of the development of ORN to help select pa琀椀ents for hypofrac琀椀onated approaches.
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