Immunotherapy

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.

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 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, 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.

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.

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 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.

Instead of attacking the cancer cell, engineering T cells to strip away the scaffolding and the suppressive immune cells that protect it.

Antibodies that switch on CD40 on dendritic cells and macrophages to kick-start an immune response against tumours that checkpoint drugs alone cannot reach.

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.

Giving the same drug at a different time of day, because the body clock changes how much damage it does and how well the immune system responds.

Cytokine therapy gives immune-signalling proteins as drugs. High-dose interleukin-2 was the first immunotherapy to cure some melanomas, at great toxicity.

Vaccines made from a patient's own antigen-presenting cells loaded with tumour proteins; sipuleucel-T for prostate cancer was the first approved, and newer versions are tested in brain and other cancers.

Patients who eat plenty of fibre and avoid probiotic pills seem to respond better to immunotherapy for melanoma, probably because fibre feeds the right gut bacteria. A proper trial is under way.

After hamster cells have grown an antibody drug, the antibody has to be fished out of a soup of cells, DNA and viruses and made pure enough to inject. Purification is where much of the cost and many of the bottlenecks of biologics sit.

Bacteria that seek out the low-oxygen core of tumours, then manufacture a drug on the spot.

Transplanting gut bacteria from patients who responded to immunotherapy into those who did not. In small studies a minority of resistant melanomas started responding. Randomised trials are running.

Destroying a tumour mechanically with sound, rather than heat, leaves the debris intact enough for the immune system to learn from it.

Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.

Most immune side effects of checkpoint inhibitors settle. The hormone glands are the exception: a pituitary, thyroid, adrenal or insulin-making gland destroyed by the immune system does not grow back, and the replacement treatment that follows is usually for life. In the follow-up cohorts 83 per cent of hormone problems were still present three months after the drug stopped.

An immune-stimulating antibody conjugate (ISAC) is an ADC whose payload wakes up the immune system inside the tumour rather than poisoning the cell.

PET scans built from radiolabelled antibodies or their fragments, to see any protein an antibody can reach, including immune cells inside tumours.

Cytokines such as interleukin-2 or TNF fused to an antibody that homes to the tumour, aiming to concentrate the immune boost where it is needed and spare the rest of the body.

Treating one tumour so aggressively that the immune system learns to attack every other one, using the tumour itself as the vaccine.

Intratumoural gene electrotransfer injects a plasmid carrying the interleukin-12 gene into a tumour and pushes it into cells with electric pulses, so this T-cell-activating cytokine is made locally instead of at the toxic doses intravenous IL-12 needed. It produced responses with pembrolizumab in anti-PD-1-resistant melanoma, but the sponsor's programmes have stalled.

Treating early bladder cancer by putting the drug straight into the bladder through a catheter, so the whole body is spared.

Antibodies against LAG-3, another brake on tired T cells; relatlimab plus nivolumab became the first approved LAG-3 combination for melanoma in 2022.

Lattice radiotherapy deliberately treats a bulky tumour unevenly, placing peaks of tumour-destroying dose at spaced points inside it while the tissue between receives far less, relying on bystander and immune effects to extend the kill. It runs on standard linear accelerators, but evidence is mostly palliative and single-arm, and the mechanism is unsettled.

Changing the gut bacteria of a patient whose immunotherapy stopped working, in the hope of restarting the response.

Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction.

An mRNA cancer vaccine is made without cells: a DNA template is copied into RNA by an enzyme in a tank, cleaned up, and wrapped in tiny fat bubbles. For personalised vaccines the whole run is done once for each patient, against that patient's own tumour mutations, in a few weeks.

Bispecific or trispecific antibodies that hold a natural killer cell against a tumour cell and switch it on, an alternative to T-cell engagers with potentially milder side effects.

Off-the-shelf cancer vaccines target antigens shared across patients, such as mutant KRAS or HER2 peptides, so they are made in advance rather than per person. Sipuleucel-T is still the only approved therapeutic cancer vaccine in the US; tolerance to self-antigens and weak past results hold them back.

Viruses engineered to infect and burst cancer cells while leaving normal cells alone, and to alert the immune system in the process.

A vaccine made for one patient, encoding the unique mutations in their own tumour, to train the immune system to hunt it.

An antibody carries a light-sensitive dye to the tumour; shining near-infrared light then bursts the cells.

Plasmid DNA and mRNA raw materials are the DNA templates and enzymes behind viral vectors and mRNA vaccines. They are invisible to patients but decisive for supply.

Antibiotics in the weeks before immunotherapy are linked with worse outcomes, and shop-bought probiotics may not help and might hurt. Avoiding both where possible is a low-cost precaution.

PSK, a protein-bound polysaccharide from the turkey tail mushroom, has been an approved adjuvant cancer drug in Japan since 1977. Meta-analyses of Japanese randomised trials in stomach and bowel cancer found a modest survival benefit added to chemotherapy, but these results have never been tested outside Japan.

RNA drugs that copy themselves inside the cell, or are made as a loop so they last longer. Both aim to get more protein from a smaller dose.

Modern biologics plants grow cells in giant sterile plastic bags instead of steel tanks, throwing the bag away after each batch. It makes plants faster to build and switch, but it ties the whole industry to a few bag and filter makers.

Sterile fill-finish is putting the finished drug into vials under sterile conditions. It is a frequent cause of shortages when capacity is tight.

Drugs that trigger the cell's built-in 'virus alarm' inside tumours to summon immune cells.

An off-the-shelf drug that physically links a killer T cell to a cancer cell, forcing the attack.

Antibodies against TIGIT, a brake on T cells and natural killer cells, tested alongside PD-L1 drugs; the biggest lung cancer trials so far have failed.

Antibodies against TIM-3, a checkpoint on exhausted T cells and myeloid cells, tested mostly with PD-1 drugs and in blood cancers.

Giving the innate immune system a memory, so monocytes and NK cells respond harder the next time they meet a tumour.

Antibodies engineered to bind three things at once, for example a tumour antigen, a T-cell activator and a co-stimulatory signal, to make a stronger or more selective immune attack.