answers
T-Cell Receptors
Are molecules on the surface of cancer fighting T cells that have the ability to interrogate individual
cancer cells and see beneath the cell membrane.
Neoantigens
• Antigens are the unique molecules or proteins that help immune cells identify and fight cancer cells.
• They are unique to each patient's tumor cells.
To design and manufacture a personalized vaccine for clinical use, what must be done?
Computer-based algorithms are used to identify which tumor-derived peptides could potentially form a
suitable tumor associated antigen (TAA) or tumor neoantigen with the patient's MHC alleles.
For example, autologous tumor cells infected with Newcastle disease virus have been used...
In one type of cancer vaccine that has demonstrated success in preclinical models of metastatic
lymphoma and melanoma.
___________ are isolated from a patient tumor biopsy and expanded ex vivo with IL-2. TILs are then
infused into a patient who has undergone lymphodepletion to provide a niche for the transferred TILs to
expand, act as effector cells and generate immunological memory.
Tumor-infiltrating lymphocytes
___________________ can direct specific cytotoxicity to a target molecule on the surface of the
malignant cell. Isolated T cells from the patient (or allogeneic donor) are genetically modified to express
CARs and then expanded and infused into the patient.
Synthetic chimeric antigen receptors (CARs)
Effects of CTLA-4 blocking antibodies
• Cytotoxic T lymphocyte antigen 4 (CTLA4)-blocking antibodies (a-CTLA4), especially when bound to an
Fc receptor (FcR) on an antigen-presenting cell (APC), can promote antibody-dependent cellular toxicity
(ADCC).
• CD4+CD25+ regulatory T (Treg) cells express higher amounts of CTLA4 than conventional T cells and
are therefore more prone to ADCC than conventional cells.
• In addition, a-CTLA4 can bind to CTLA4 on the surface of the Treg cell and prevent it from counter-
regulating the CD28-mediated co-stimulatory pathways that are playing a role in T cell activation.
• At the same time, a-CTLA4 can also promote T cell responses by blocking CTLA4 on the surface of
conventional T cells as they undergo activation.
FDA approved CAR-T Cell Therapy:
, • Axicabtagene ciloleucel
• Brexucabtagene autoleucel
• Idecabtagene vicleucel
• Lisocabtagene maraleucel
• Tisagenleucel
• Citacabtagene autoleucel
CTLA-4 inhibitors
• Ipilimumab (with or w/o nivolumab)
• Tremelimumab (with or w/o durvalumab)
Tremelimumab + Durvalumab
For the unresectable hepatocellular carcinoma and non-small cell lung cancer.
PD1/PDL1 blockade in cancer
• Activated T cells express programmed cell death 1 (PD1), which engages with its specific ligand (PDL1
and PDL2) to dampen activation.
• Blocking of the PD1 axis through the administration of an anti-PD1 (or anti-PDL1 or anti-PDL2)
antibody prevents this inhibitory interaction and unleashes antitumoral T lymphocyte activity by
promoting increased T cell activation and proliferation, by enhancing their effector functions and by
supporting the formation of memory cells.
• Consequently, more T cells bind to tumor antigens presented on tumor cells by MHC molecules via
their T cell receptors (TCRs).
• This ultimately leads to the release of cytolytic mediators, such as perforin and granzyme, causing
enhanced tumor killing.
Immune checkpoints engage when proteins on the surface of immune cells called T cells recognize and
bind to partner proteins on other cells, such as some tumor cells. These proteins are called
____________.
immune checkpoint proteins
When the checkpoint and partner proteins bind together, they send an ________ to the T cells.
"off" signal
PD-1 inhibitors
• Nivolumab
• Pembrolizumab
• Cemiplimab
• Dostarlimab
PD-L1 inhibitors
• Atezolizumab
• Avelumab
• Durvalumab