Teaching pack: Cell Therapy

Cell therapy covers treatments in which immune cells are taken from a patient or a donor, engineered or expanded, and given back as a living drug. CAR-T has transformed B-cell malignancies and myeloma, and solid tumours are the frontier, with TIL therapy such as lifileucel, TCR-T such as afamitresgene, CAR-T against CLDN18.2 and GPC3, armoured and logic-gated CARs, allogeneic and in vivo CAR-T delivered by targeted LNPs carrying CAR mRNA, and CAR-NK and CAR-macrophages. The section lists cell-therapy release and potency testing and is linked from CAR-T, in vivo CAR-T, TIL therapy, TCR-T, CAR-NK and CAR-macrophage, allogeneic cell therapy, CAR-T for glioma, stem cell transplantation, and the companies Autolus Therapeutics and US WorldMeds.

• Allogeneic (off-the-shelf) cell therapy: Cell therapies made from healthy donors in advance, so patients do not have to wait for their own cells to be engineered.
• Allogeneic cell banks: one donor, hundreds of doses: Instead of making CAR-T cells from each patient, take T cells from a healthy donor or from a stem cell line, edit them so the patient's body will not fight them, grow a huge batch and freeze it into hundreds of doses that sit on a shelf.
• Allogeneic donor and iPSC master cell banks: Making cell therapies from a healthy donor or stem-cell line in advance, so patients get an off-the-shelf product instead of waiting weeks.
• Allogeneic stem cell transplantation: Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.
• Apheresis and starting-material collection: Apheresis is collecting a patient's white blood cells through a machine over several hours. Every autologous CAR-T begins here, and the quality of these cells shapes the final product.
• Armoured, logic-gated & next-gen CARs: Upgraded CAR-T cells that also secrete immune boosters, resist exhaustion, or only fire when two signals are present.
• Autologous CAR-T manufacturing, batch by batch: Each CAR-T dose is a separate factory run for one patient: collect their T cells, activate them, add the CAR gene with a virus, grow them for a week or two, freeze, test and ship them back. The steps, the failure points and the waiting list are all here.
• Autologous stem cell transplant (high-dose therapy): Autologous stem cell transplant collects the patient's own blood-forming stem cells, gives melphalan or another chemotherapy at a dose that would otherwise destroy the marrow, then returns the cells to rebuild it. It is standard consolidation in myeloma and for relapsed lymphoma, though CAR-T has displaced it in early-relapsing large B-cell lymphoma.
• CAR-NK & CAR-macrophage: Putting the cancer-seeking receptor on natural killer cells or macrophages instead of T cells, which could be safer and off-the-shelf.
• CAR-T against stroma: fibroblasts and myeloid cells: Instead of attacking the cancer cell, engineering T cells to strip away the scaffolding and the suppressive immune cells that protect it.

• Allogeneic regulatory T cell immunotherapy with HSPC and T cells-vldq (approved): Tregzi, formerly Orca-T, is a donor stem cell transplant sorted with high precision and given with regulatory T cells, so that patients with blood cancers keep the graft's anti-cancer effect while being protected from chronic graft-versus-host disease. The FDA approved it on 30 June 2026 for adults having a matched-donor transplant.
• Omidubicel (approved): An expanded umbilical cord blood graft that shortens the dangerous wait for neutrophils to return after a transplant for blood cancer, the first cell therapy approved to speed engraftment.
• Remestemcel-L (approved): Donor bone marrow stromal cells given to children whose acute graft-versus-host disease no longer responds to steroids, the first mesenchymal stromal cell therapy approved in the United States.

• Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR · Foundations (historic)
• Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR · CD19 and BCMA CAR-T approved (historic)
• Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR · Solid tumours: TIL, TCR-T, CAR-T (current)
• Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR · Manufacturing revolution: allogeneic and in vivo (emerging)
• Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR · Speculative (speculative)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Two viruses, found because lymphoma is the cancer you can get hold of (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · How little is enough: the Hodgkin de-escalation programme begins (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Reading the genes, and the twenty years it took to make that useful (historic)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Everything that failed to beat R-CHOP, and the one thing that did (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · The scan after two cycles, and what it is good for (current)
• Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting · Indolent lymphoma: how long to treat, and the two-year mark that splits the disease (current)
• Paths to cures: interception, eradication, control · What already prevents cancer (historic)
• Paths to cures: interception, eradication, control · Vaccinating and monitoring people who do not yet have cancer (emerging)
• Paths to cures: interception, eradication, control · Removing every cell, and knowing that you did (current)
• Paths to cures: interception, eradication, control · Killing the last cell, wherever it is hiding (emerging)
• Paths to cures: interception, eradication, control · Living with cancer as a chronic disease (current)
• Paths to cures: interception, eradication, control · Steering resistance instead of waiting for it (emerging)
• Radical oncology: what could change the war by 2035 · Ideas already being tested against a control arm (current)
• Radical oncology: what could change the war by 2035 · Living drugs, logic gates, and designed proteins reach decision points (emerging)
• Radical oncology: what could change the war by 2035 · Radiation and radiopharmaceuticals get a second act (emerging)
• Radical oncology: what could change the war by 2035 · Monitoring becomes continuous and selection becomes spatial (emerging)
• Radical oncology: what could change the war by 2035 · Writing to the genome and the epigenome inside a tumour (speculative)
• Radical oncology: what could change the war by 2035 · Treating the soil rather than the seed (speculative)

• PERSEUS (phase 3, n=709): Progression-free survival at 48 months: 84.3% vs 67.7%, HR 0.42
• ZUMA-7 (phase 3, n=359): Event-free survival (median): 8.3 months vs 2 months, HR 0.4
• CARTITUDE-4 (phase 3, n=419): Progression-free survival: pending
• LyMa (phase 3, n=240): Event-free survival at 4 years: 79% vs 61%
• TRANSFORM (phase 3, n=184): Event-free survival (median): 29.5 months vs 2.4 months, HR 0.36
• AETHERA (phase 3, n=329): Progression-free survival (median): 42.9 months vs 24.1 months, HR 0.57

1. What is the first approved TIL therapy and how well does it work?
   Answer

   Lifileucel (Amtagvi, Iovance), approved 2024 for anti-PD-1-refractory melanoma: response rate about 31%, with roughly a third of responders still responding at five years.
2. What is CAR-T and which cancers is it approved for?
   Answer

   A patient's T cells are engineered with a synthetic receptor, multiplied, and returned. Approved CD19 products treat B-cell lymphomas and leukaemias; BCMA products treat multiple myeloma; the first solid-tumour approval (Claudin 18.2, gastric) is in China.
3. What is in vivo CAR-T and why is it exciting?
   Answer

   Targeted lipid nanoparticles or viral vectors deliver CAR-encoding mRNA or DNA to T cells inside the patient, avoiding manufacturing, lymphodepletion, and wait time and allowing redosing; first-in-human data in 2025-26 show B-cell depletion. AbbVie bought Capstan for up to $2.1B.

• NCI: T-cell transfer therapy: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/t-cell-transfer-therapy