Company: DRTSW
Filing Date: 2025-03-12
Form Type: 20-F
Source: 0001213900-25-023187
Chunk: 145

Company: Alpha Tau Medical Ltd.
Filing Date: 2025-03-12
Form: 20-F
Item: Item 4
Chunk 145
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 then interact with tumor
antigens and then migrate to the lymph nodes where they present antigens to T cells, a process that is mediated by the MHC pathway and
other co-stimulatory signals, such as CD80 and CD28. After activation by multiple signals, T cells, especially the CD8+ T cells, may be
activated and begin to propagate. As a result, activated effector T cells may exit the lymph nodes and home to tumors, including primary
tumors and non-irradiated tumor metastases, to exert their effect of killing tumor cells. However, cytotoxic T lymphocyte-associated antigen
4 (CTLA-4) competitively combines with CD80/86 and inhibits the activation of T cells. Following T cell activation, programmed cell death
1 (PD-1) receptors that are expressed on the T cell surface bind primarily to PD-L1 and inhibit immune responses. Hence, we believe the
administration of immune checkpoint blockades of CTLA-4, PD-1, and PD-L1 may be able to enhance the anti-tumor immunity induced by radiotherapy.

Source: Journal of Hematology & Oncology
available at: https://pubmed. ncbi. nlm. nih. gov/30115069/

Previously reported studies
have demonstrated that ablation treatments, such as radiotherapy, have the potential to expose the body to large amounts of tumor antigens
and danger signals and thus may trigger anti-tumor immunity. Consistent with this thesis, we observed that Alpha DaRT rendered studied
animals resistant to a second tumor challenge in two tumor models, colon carcinoma and breast carcinoma. In the immunogenic colon carcinoma
tumor model CT26, mice that were treated with Alpha DaRT developed resistance to tumor re-challenge in the opposite lateral side of the
back or to experimental metastases in the lungs, suggesting that a systemic immune memory was induced following treatment. The figure
below demonstrates the tumor development (A) and survival (B) of mice who were challenged with CT26 cancer cells, where those mice were
previously treated for CT26 tumors with Alpha DaRT or with inert sources, compared to naïve mice that did not previously have tumors.

Inhibition of regulatory T
cells by low-dose cyclophosphamide, inhibition of Myeloid-derived Suppressor Cells, or MDSCs, by sildenafil, or immuno-stimulation by
CpG further enhanced the tumor retardation induced by Alpha