Science & Technology
APPROACH

Novel Platform for Autologous Cell Therapy

Cancer patients – all of them – have a powerful, natural source of tumor-targeting immune cells that can fight cancer. WindMIL is the only company that can activate and expand these naturally occurring cells into marrow-infiltrating lymphocytes (MILs™), transforming them into a novel, next-generation cancer-fighting cell therapy.

Our scientific founders discovered that the bone marrow of cancer patients holds a natural reservoir of memory T cells that can recognize, find and eliminate cancer cells. Our technology collects, activates and expands these memory T cells into MILs, creating a flexible, scalable, wide-ranging, transformative platform for autologous cell therapy.

Collecting bone marrow containing these memory T cells is straightforward and completed via a short outpatient procedure. From this, WindMIL uses a standardized, patent-protected activation and expansion process to create therapeutic MILs quickly and efficiently.

The Importance of Cell Source
in Cell Therapy

The advantage of MILs as a cell therapy platform for all types of cancers stems from their derivation from memory T cells in bone marrow. The bone marrow has an important role in the immune system, acting as a reservoir of persistent immune cells generated as a response to foreign antigens. Because memory T cells in bone marrow occur as a result of the response to a patient’s unique cancer, MILs formed from them are primed to find and kill that patient’s cancer. These unique properties found in bone marrow T cells allow MILs to be grown for any patient, for any tumor type — hematologic or solid. Evidence suggests that MILs could be activated to recognize and treat numerous solid tumor cancers, including lung, bladder, breast, glioblastoma, head and neck, melanoma, sarcoma, prostate, renal cell, hepatocellular and others.

 

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Cell Source MattersTM

WindMIL has a simple but profound premise: Cell Source Matters in cell therapy. Due to their derivation from bone marrow, MILs naturally exhibit a set of differentiating features that make them an optimal source of cancer-killing T cells for use in all oncology cell therapies.

  • Naturally tumor-specific – they recognize and destroy a broader spectrum of cancer cells
    • Our MILs platform is based on antigen-experienced memory T cells that have already spotted the intruding cancer and therefore, are naturally primed to recognize and destroy a patient’s cancer cells once activated and expanded.
    • MILs are polyclonal, enabling them to mount a broader attack on the cancer than peripheral blood lymphocytes (PBLs), which are the current standard for cell therapy. This broad recognition helps thwart cancer’s ability to eventually evade the body’s immune response.
  • Highly cytotoxic
    • The cellular phenotype of MILs — activated antigen experienced memory T cells — makes them highly efficient killers of cancer cells.
    • MILs also target a broader spectrum of cancer cells than PBLs. MILs recognize and destroy both mature tumor cells as well as their self-renewing precursors.
  • Highly persistent
    • The ability to persist over a significant time and continue to kill cancer is a key component in cell therapy clinical responses. MILs persist significantly longer than adoptive T-cell therapies from other cell sources due to their memory phenotype, with clinical trials seeing up to eight years of activity post-infusion.

MILs have extraordinary potential to transform autologous cell therapy and cancer treatment. Harnessing cells naturally generated by the immune system, MILs strongly exhibit the hallmarks necessary for a truly robust cell therapy. They are accessible and capable of being activated and expanded; they naturally recognize and target a broad spectrum of cancer cells; and they are powerful tumor cell killers and persist in their ability to fight cancer.

Matched MILsTM vs. PBLs Tumor Specificity

Measured by Intracellular Cytokine-Staining

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Tumor antigen-specific T cells are present in MILsTM but absent in activated PBLs. Tumor antigen-specific T cells were quantitated in MILsTM and peripheral blood lymphocytes (PBLs) activated and expanded from the bone marrow and blood of four metastatic prostate cancer patients using a previously described functional assay (Noonan KA,et al. Sci. Transl. Med. 2015;7(288):288ra78). Briefly, autologous bone-marrow-derived antigen-presenting cells (APCs) were pulsed with lysates from prostate cancer cell lines (“matched tumor lysate”) and co-cultured for five days with CFSE-labelled MILsTM or PBLs. CFSE-labelled MILsTM and PBLs were separately co-cultured with APCs pulsed with multiple myeloma cancer cell line lysates (“Unmatched Tumor Lysate”) or media alone (“No Lysate”) as specificity controls. At the end of the 5-day co-culture, intra-cellular cytokine staining was used to measure IFNg effector cytokine-production in dividing CD3+ T cells. The mean percentage of IFNg-producing CFSE-low CD3+ T cells detected in MILsTM and PBLs are shown for each condition. Effector cytokine-producing tumor antigen-specific T cells were only detected in MILsTM, and only in response to the matched tumor lysate. Although not shown here, this has been demonstrated for other tumor types as well, including multiple myeloma and non-small cell lung cancer.

MILsTM Result in Complete Clearance of Myeloma in Animals

 

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Treatment with MILsTM results in complete clearance of multiple myeloma in mice. Immunocompromised NOD/SCID mice (10 mice per group) were challenged with the human NIH929 multiple myeloma cell line and followed for 30 days until human kappa light chain secreted by the NIH929 tumor cells was detected in blood consistent with tumor engraftment. The tumor-bearing mice were then treated with either activated peripheral blood lymphocytes (“aPBL”) or MILsTM (“MIL”) generated from the same multiple myeloma patient, or with vehicle alone as a mock treatment control (“HBSS”). Tumor burden was followed in the treated and mock treated mice by measuring the level of human kappa light chain in blood. Only treatment with MILsTM resulted in tumor-regression and clearance.