Teaching pack: Immunotherapy

This section gathers the treatments that work by getting the patient's own immune system to recognise and destroy the cancer rather than attacking the tumour directly with a drug. It covers checkpoint inhibitors against PD-1, PD-L1, CTLA-4 and LAG-3, bispecific T-cell engagers, cancer vaccines including personalised mRNA neoantigen vaccines, oncolytic viruses, cytokines and innate-immune agonists. Two problems dominate: working out in advance who will respond, and converting cold tumours into hot ones. Technology entries filed here include Monoclonal antibodies, Bispecific antibodies, Immuno-PET and Intravesical therapy, and companies placed in the section include Incyte, ImmunityBio, CG Oncology, Ferring Pharmaceuticals, Y-mAbs Therapeutics and Shanghai Henlius Biotech.

• Antibody manufacturing (CHO bioprocessing): Antibody manufacturing means growing antibody drugs like pembrolizumab or trastuzumab in vats of engineered hamster cells, then purifying them. It is the industrial base for most modern cancer drugs.
• Bacterial vector cancer vaccines: Weakened bacteria such as Listeria engineered to carry tumour antigens, using the body's strong response to infection to train T cells against cancer.
• Bacteriophage-based tumour delivery: Bacteriophage delivery uses viruses that infect bacteria, not human cells, as engineered shells whose coat proteins display tumour-homing peptides or antigens and carry drugs or vaccines. They are cheap and cannot replicate in people, but the work is preclinical: no oncology phage trial had reported efficacy by 2026, and the body clears them quickly.
• BCG manufacturing and the bladder cancer BCG shortage: BCG, the century-old tuberculosis vaccine, is the best treatment for early bladder cancer, but it is a live bacterium that grows slowly and only one company makes it for the United States. Since 2019 urologists have been splitting doses and rationing courses.
• Biosimilar manufacturing and comparability: A biosimilar is a copy of an antibody drug made by a different company in different cells. It cannot be identical, so the maker must prove the copy behaves the same in the laboratory and in patients. Biosimilars of trastuzumab, bevacizumab and rituximab have cut the cost of these drugs sharply.
• Bispecific antibodies: A bispecific antibody is one antibody with two different grabbing arms, so it can block two targets at once or pull an immune cell onto a cancer cell.
• Cancer interception vaccines: Cancer interception vaccines immunise people who do not yet have cancer but carry a high inherited risk, such as Lynch syndrome carriers, against the antigens their future tumour is predicted to express, so memory T cells remove transformed cells early. Because healthy people accept risk for a probabilistic benefit, the safety bar is far higher and trials take years.
• 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.
• CD40 agonist antibodies: Antibodies that switch on CD40 on dendritic cells and macrophages to kick-start an immune response against tumours that checkpoint drugs alone cannot reach.
• CD47 and SIRP-alpha blockade: Drugs that remove the 'don't eat me' signal cancer cells show to macrophages, so the immune system's scavenger cells can engulf them; the lead programme was halted for safety.

• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · A cancer with a visible precursor, and the first proof that finding it early saves lives (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Total mesorectal excision, and radiotherapy before the operation (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Chemotherapy after the operation, and how small the benefit is when the nodes are clear (historic)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · The screening programmes, and the discovery that uptake is the whole game (current)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · Antibodies, and the two things that decide whether they work (current)
• Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation · The genome, the subtypes and the hypermutated sixth (historic)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · Surgery arrives, and the cancer is found by accident (historic)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · Staging by depth, then by side (historic)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · The incidental cancer pathway: re-resect from T1b, but who, when and how much (current)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · A borrowed chemotherapy standard (historic)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · Adjuvant capecitabine and second-line FOLFOX, from UK trials (current)
• Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials · Radiotherapy: one single-arm trial and a nomogram (historic)
• Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity · Prehistory (historic)
• Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity · Checkpoint revolution (historic)
• Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity · Earlier lines and combinations (current)
• Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity · Engineered immunity arrives (emerging)
• Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity · Speculative (speculative)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · The cause is named, and cancer epidemiology is invented to name it (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Cytotoxic chemotherapy, and the ceiling it hit (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · EGFR, ALK, and the invention of precision oncology in solid tumours (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Low-dose computed tomography earns its place, and chest radiography loses its (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Immunotherapy, and the trouble with PD-L1 as a gate (historic)
• Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch · Stage III, and treatment moving to either side of the operation (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 · 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)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · One operation, and still the only cure (historic)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · A blood marker with a blind spot and an oncogene in nearly every tumour (historic)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · Gemcitabine, and chemotherapy after surgery (historic)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · Combination chemotherapy for metastatic disease (historic)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · Genomes, subtypes and the inherited five percent (historic)
• Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question · Adjuvant modified FOLFIRINOX, and the neoadjuvant question (current)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · Chemotherapy only (historic)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · Immunotherapy and PARP arrive (historic)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · Curative setting transformed (historic)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · ADCs move to first line; bispecific ADC succeeds (current)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · Next: residual disease, de-escalation, selection (emerging)
• TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line · Speculative: cure for most, control for the rest (speculative)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · Defined by three negative tests (historic)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · The basal-like subtype and its link to BRCA1 (historic)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · Founder mutations: hereditary disease has a geography (historic)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · A name, a natural history and a disparity (historic)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · Anthracycline and taxane chemotherapy, and the residual disease paradox (historic)
• Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem · Several diseases: molecular subtypes (historic)

• CheckMate 649 (phase 3, n=1,581): Overall survival, PD-L1 CPS ≥5: 14.4 months vs 11.1 months, HR 0.71
• KEYNOTE-042 (phase 3, n=1,274): Overall survival, PD-L1 tumour proportion score 50% or more: 20 months vs 12.2 months, HR 0.69
• KEYNOTE-859 (phase 3, n=1,579): Overall survival, all randomised: 12.9 months vs 11.5 months, HR 0.78
• CASPIAN (phase 3, n=805): Overall survival: 13 months vs 10.3 months, HR 0.73
• CheckMate 214 (phase 3, n=1,096): Overall survival, intermediate/poor risk (8-year follow-up): pending
• CheckMate 648 (phase 3, n=970): Overall survival, PD-L1 ≥1% (nivolumab + chemotherapy): 15.4 months vs 9.1 months, HR 0.54

1. What was the first personalised cancer vaccine to win a phase 3 trial?
   Answer

   Intismeran autogene (V940/mRNA-4157, Moderna/Merck) with pembrolizumab in resected stage IIB-IV melanoma: INTerpath-001 met recurrence-free and distant-metastasis-free survival, announced 19 August 2026.
2. How is a personalised mRNA cancer vaccine made?
   Answer

   The tumour and normal DNA are sequenced, software predicts up to 34 neoantigens unique to the tumour, a patient-specific mRNA encoding them is manufactured in lipid nanoparticles over about six weeks, and it is given with a PD-1 blocker.
3. What are the main side effects of checkpoint inhibitors and how are they handled?
   Answer

   Immune-related adverse events such as colitis, thyroid problems, rash, hepatitis, and pneumonitis, most common with CTLA-4 plus PD-1 combinations; treated with steroids and sometimes other immunosuppressants, some endocrine effects are permanent.
4. Name three next-generation ADC concepts beyond bispecific antibodies.
   Answer

   Dual-payload ADCs, degrader-antibody conjugates, immune-stimulating antibody conjugates, masked or conditionally active ADCs, peptide-drug conjugates, radio-ADCs.
5. Why might personalised vaccines work better after surgery than in metastatic disease?
   Answer

   Tumour burden is low so immune responses are not overwhelmed, there is time for the six-week manufacturing, immunosuppression from bulky disease is absent, and recurrence-free survival is a clean endpoint; INTerpath-001 tested exactly this adjuvant setting.

• NCI: Immunotherapy to treat cancer: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy