NorthWest Biotherapeutics Inc (NWBO)

[Red_Right_Hand]

Generalizable?

“A key difference between tissue agnostic oncology drug development and traditional oncology drug development is the inherent need in tissue agnostic drug development to generalize treatment effects based on data observed in some cancer types to other cancer types with the same targeted molecular alteration, when no subjects (or a limited number of subjects) with the other cancer types were included in the clinical trial(s). As described further in this guidance, such generalization may be justified, in appropriate cases, by a strong scientific rationale and clinical circumstances….” (Lines 59-65, draft Guidance; https://www.fda.gov/media/162346/download)

Do reports in the scientific literature support a strong scientific rationale that the tumor lysate-pulsed autologous dendritic cell vaccine approach is generalizable across diverse tumors/tissues, as evidenced by where that approach has been attempted?

“For indications where surgery can be performed as part of treatment, a common approach to antigen loading has been the use of tumor lysates as a source of antigen.” (https://insights.bio/cell-and-gene-therapy-insights/journal/article/2095/Towards-the-rational-design-of-a-next-generation-dendritic-cell-vaccine-for-cancer-immunotherapy; see also https://www.futuremedicine.com/doi/full/10.2217/imt-2022-0036)

Sarcoma: https://academic.oup.com/noa/article/3/1/vdab027/6133441;

Colorectal cancer: https://www.sciencedirect.com/science/article/abs/pii/S1043661820316820

Breast cancer: https://link.springer.com/article/10.1007/s00262-011-1192-2

Glioma: https://aacrjournals.org/cancerres/article/64/14/4973/511479/Vaccination-with-Tumor-Lysate-Pulsed-Dendritic

Melanoma: https://journals.lww.com/immunotherapy-journal/Abstract/2008/01000/Analysis_and_Characterization_of_Antitumor_T_cell.12.aspx

Liver: https://journals.lww.com/immunotherapy-journal/Abstract/2005/09000/Vaccination_of_Advanced_Hepatocellular_Carcinoma.9.aspx; https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.22626

Prostate: https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0045(199601)28:1%3C65::AID-PROS9%3E3.0.CO;2-N

Acute Myelogenous Leukemia: https://onlinelibrary.wiley.com/doi/abs/10.1002/jca.10080; https://pubmed.ncbi.nlm.nih.gov/29632738/
Parathyroid carcinoma: https://eje.bioscientifica.com/view/journals/eje/142/3/300.xml

Ovarian: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-02133-w

Kidney: https://aacrjournals.org/clincancerres/article/8/11/3369/289270/Immunotherapy-of-Metastatic-Renal-Cell-Carcinoma

Glioblastoma: https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847

Agnostic?

“A polyclonal but antigen agnostic approach includes the use of autologous whole cell tumour vaccines or tumour lysates, which provide the entire repertoire of a patients’ tumour antigens including mutated neoepitopes without the need for identification of individual antigens. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282323/)

“T-cell therapies can be antigen agnostic (administered without precise knowledge of the antigens targeted), such as in unmanipulated donor lymphocyte infusions (DLI) and TIL infusion, or targeted to known antigens.” https://www.frontiersin.org/articles/10.3389/fimmu.2020.00276/full

“… many prefer the concept of antigen-agnostic immunotherapies that allow each patient’s immune system to determine its own antigen specificities.” https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(19)30015-4