Glossary

Bioinformatics

The use of software and algorithms to analyze biological data. In personalized cancer vaccines, bioinformatics pipelines (such as pVAC-Seq) compare the tumor's DNA to the patient's healthy DNA to identify which mutations are most likely to be recognized by the immune system.

Used in: Providers & Labs (step 2 of the provider chain)

Breakthrough Therapy Designation

An FDA designation that speeds up the development and review of a drug intended to treat a serious condition where early clinical evidence shows substantial improvement over existing treatments. Moderna/Merck's intismeran autogene has this designation for adjuvant melanoma. It does not mean the drug is approved.

Source: FDA Breakthrough Therapy

Checkpoint Inhibitor

A type of immunotherapy drug that releases the "brakes" on the immune system, allowing T-cells to attack cancer more aggressively. Common checkpoint inhibitors include pembrolizumab (Keytruda) and nivolumab (Opdivo). Personalized cancer vaccines are often administered alongside checkpoint inhibitors to enhance the immune response.

Used in: Research (Moderna/Merck trial used pembrolizumab + vaccine)

Source: NCI Dictionary

Clinical Trial Phases

Clinical trials proceed through numbered phases before a drug can be approved:

• Phase 1: Tests safety and dosing in a small group (typically 15-30 patients). Not designed to prove the drug works.
• Phase 2: Tests whether the drug works and continues to monitor safety (typically 30-300 patients).
• Phase 3: Compares the drug to the current standard of care in a large group (typically hundreds to thousands). Required for FDA approval.

Context: Moderna/Merck is in Phase 3. Mount Sinai's PGV001 completed Phase 1.

Source: NCI Dictionary

CMO (Contract Manufacturing Organization)

A company that manufactures pharmaceutical products on behalf of another company or organization. In personalized cancer vaccines, CMOs like CSBio and GenScript build the custom vaccine in GMP-certified facilities. Each patient's vaccine is a unique batch.

See: Vaccine Manufacturers

ECOG Performance Status

A scale used by physicians to measure how well a patient can carry out daily activities. It runs from 0 to 5:

Most expanded access programs require ECOG 0-2. Patients who decline to ECOG 3 or below during the vaccine manufacturing period may become ineligible for treatment.

Used in: Eligibility Checker

Source: ECOG-ACRIN Cancer Research Group

Expanded Access (Compassionate Use)

An FDA regulatory pathway that allows patients with serious or life-threatening conditions to use investigational treatments that have not yet been approved. Authorized under Section 561 of the Federal Food, Drug, and Cosmetic Act. A licensed physician files an Investigational New Drug (IND) application on the patient's behalf. The FDA approves over 99% of individual patient requests.

This is the pathway used for personalized cancer vaccines today. Full guide: Expanded Access Guide

Source: FDA Expanded Access

GMP (Good Manufacturing Practice)

A set of regulations enforced by the FDA (and equivalent agencies worldwide) that ensure pharmaceutical products are consistently produced and controlled according to quality standards. For personalized cancer vaccines, GMP manufacturing means the vaccine is built in a certified cleanroom (ISO 7 minimum) with sterility testing, chain-of-identity tracking, and validated analytical methods for peptide purity (typically above 95%).

See: Vaccine Manufacturers

Source: FDA cGMP Regulations

HLA Typing

HLA (Human Leukocyte Antigen) typing identifies the specific proteins on the surface of your cells that present fragments of mutated proteins to the immune system. Different people have different HLA types, which means the same mutation might be a good vaccine target for one patient but not another. HLA typing is a critical step in neoantigen prediction — it determines which mutations your specific immune system is capable of recognizing.

Used in: Providers (CeGaT CancerNeo includes HLA typing)

Source: NCI Dictionary

IND (Investigational New Drug) Application

A request submitted to the FDA before an investigational drug can be administered to humans. For expanded access, physicians file an individual patient IND using the simplified Form FDA 3926 (a single-page form). The FDA typically responds within 30 days, though emergency INDs can be authorized by phone within 24 hours.

Full details: Expanded Access Guide

Source: FDA IND Applications

mRNA Vaccine

A vaccine that uses messenger RNA (genetic instructions) to teach your cells how to make a specific protein — in this case, the neoantigen targets from your tumor. Your cells produce the proteins temporarily, the immune system learns to recognize them, and then the mRNA breaks down. Moderna/Merck's intismeran autogene is an mRNA-based personalized cancer vaccine. This is the same technology platform used in COVID-19 vaccines, adapted for cancer.

See: Research (Moderna/Merck trial results)

Neoantigen

A protein fragment produced by a mutation that is unique to a patient's tumor and does not exist in their healthy cells. Because neoantigens are foreign to the body, the immune system can learn to recognize and attack cells that display them. Personalized cancer vaccines work by training the immune system to target specific neoantigens identified through genomic sequencing of the tumor.

This is the core concept behind personalized cancer vaccines. See: How It Works

Source: NCI Dictionary

Peptide Vaccine

A vaccine made from short chains of amino acids (peptides) that match the neoantigen targets from a patient's tumor. Unlike mRNA vaccines that instruct cells to produce proteins, peptide vaccines deliver the protein fragments directly. The Jaime Leandro Foundation's expanded access program uses peptide-based personalized vaccines manufactured by CSBio.

See: Providers (JLF partner chain)

Personalized Cancer Vaccine (Neoantigen Vaccine)

An immunotherapy custom-built for one patient that targets the unique mutations (neoantigens) in that patient's tumor. The process involves sequencing the tumor's DNA, identifying the best neoantigen targets using bioinformatics, manufacturing a vaccine (peptide or mRNA) encoding those targets, and administering it as a series of injections. Each vaccine is one-of-a-kind. The entire process takes approximately 4-5 months.

Full overview: How It Works | FAQ

Right to Try Act

A federal law (21 USC 360bbb-0a) that allows terminally ill patients to access investigational drugs that have completed a Phase 1 clinical trial without FDA pre-authorization. This does not apply to personalized cancer vaccines because each vaccine is unique to one patient and has never been through Phase 1 testing on anyone. The expanded access pathway is used instead. Some states (New Hampshire, Texas) are introducing legislation to extend right-to-try to individualized treatments.

Detailed comparison: FAQ — Legal

Source: Right to Try Act (S.204)

Tumor Mutational Burden (TMB)

A measure of how many mutations a tumor has in its DNA. Cancers with higher TMB have more mutations, which means more potential neoantigen targets for a personalized vaccine. TMB is usually measured as mutations per megabase of DNA sequenced. Higher TMB generally correlates with better response to immunotherapy, though it is not a guarantee.

Relevant to: Eligibility (higher TMB may improve vaccine effectiveness)

Source: NCI Dictionary

Whole Exome Sequencing (WES)

A laboratory process that reads all the protein-coding regions of a patient's DNA (the "exome" — approximately 1-2% of the total genome, but contains about 85% of known disease-causing mutations). In personalized cancer vaccines, WES is performed on both the tumor and a healthy tissue sample. Comparing the two reveals mutations unique to the cancer. This is the foundation of neoantigen identification.

WES costs approximately $1,100-$2,800 for self-pay patients, depending on sequencing depth.

See: Sequencing Labs (Tempus xE and CeGaT CancerNeo both use WES)