Immunotherapy nomenclature

1. PROF.S.SUBBIAH et al.
IMMUNOTHERAPY
NOMENCLATURE
Department of Surgical Oncology
Centre for Oncology
GRH,Royapettah

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DEFINITION
• It is also called as BIOLOGICAL THERAPY or
BIOTHERAPY
• Immunotherapy or biological therapy is a modality
of treating a disease by activating or suppressing
the immune system.
• Immunotherapies designed to elicit or amplify an
immune response are classified as activation
immunotherapies, while immunotherapies that
reduce or suppress are classified as suppression
immunotherapies.

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HISTORY
• William B. Coley, MD, now known as the Father of
Immunotherapy, first attempted to harness the
immune system for treating cancer in the late 19th
century.
• He developed Coley toxins.
• Coley achieved response in several types of
malignancies, including sarcoma, lymphoma, and
testicular carcinoma
• But he failed to explain mechanism

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• The first immunotherapy agent, an antitumor
cytokine called interferon-alpha 2 (IFN-a2), was
approved by the US Food and Drug Administration
(FDA) in 1986.
• The first mAb approved for clinical use in the USA
and European union was for a mouse sequence
mAb against the CD3 antigen and was named
muromonab-CD3

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INTERNATIONAL
NONPROPRIETARY NAME
• INN system begun in 1950 by the World Health
Organization (WHO) to provide a unique (generic)
name to identify each pharmaceutical substance.

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• INN typically begin with a fantasy prefix and
terminate with a suffix that indicates the
pharmacological nature of the drug. The suffix is
selected as an official stem when a group of
pharmacologically related substances is named
with a common suffix.

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• Example suffix
• mab - for all MONOCLONAL ANTIBODIES
• cept for all receptor group

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MONOCLONAL
ANTIBODIES
NOMENCLATURE

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MONOCLONAL ANTIBODIES
• INN for a mAb comprised a fantasy prefix, which
contributes to a euphonious and distinctive name;
• Followed by a substem A (also known as infix A),
which indicates the target (molecule, cell or organ)
class of the mAb;
• Followed by a second substem, substem B (or infix
B), which indicates the species on which the
immunoglobulin sequence of the mAb is based;
• Finally by the stem

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• TRASTUZUMAB
• TRAS - DISTINCT NAME
• TU - TARGET (TUMOR)
• ZU - SPECIES OF ORIGIN
MAB - STEM

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PREFIX A -TARGET CLASS

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PREFIX B - ORIGIN SPECIES

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MAB STRUCTURE

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As per American medical association definition a
chimeric Antibodies is one in which sequence
analysis of variable regions showing less than 85
Percentage of human content.
Eg CETUXIMAB.

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WHO DEFINITION FOR
HUMANISED ANTIBODY
• “A humanized antibody is one for which both chain
types are humanized as a result of antibody
engineering.
• A humanized chain is typically a chain in which the
complementarity determining regions (CDR) of the
variable domains are foreign(originating from one
species other than human, or synthetic) whereas
the remainder of the chain is of human origin.

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• American Medical Association provides definition
of human antibodies based on sequence identity.
Sequence threshold for humanised
designation was apparently reduced from 90% to
≥85%.

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HUMAN
•Both heavy and light chains and it's
variable domains resembles exactly as
that of human.

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Common examples
• Chimeric -xi Abciximab, Rituximab, Infliximab,
Cetuximab
• Humanized -zu Palivizumab, Trastuzumab,
Bevacizumab, Natalizumab
• Human -u Adalimumab, Panitumumab Golimumab,
Ipilimumab

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GENE THERAPY
NOMENCLATURE

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• The INN nomenclature scheme for gene therapies
first adopted In 2005 and updated in 2016.

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• The scheme covers substances based upon
recombinant nucleic acid sequences involving viral
and bacterial vectors and plasmid DNA.
• It involves a two-word system where the first Word
indicates the relevant gene component while the
second word identifies the vector component.

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GENE COMPONENT(WORD 1)
• The suffix for the first word is gene with a
preceding infix identifying the gene of
interest/target gene.
• PREFIX- Random, to contribute to euphonious and
distinctive name.

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INFIX
• cima- cytosine deaminase gene
• -ermin- growth factor
• -kin- interleukin
• -lim- immunomodulator
• -lip- human lipoprotein lipase
• -mul- multiple gene
• -stim- colony stimulating factor
• -tima- thymidine kinase
• -tusu- tumour suppression

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VECTOR COMPONENT - SECOND
WORD
PREFIX ----- INFIX------ SUFFIX
Prefix ~Random distinct name.
Suffix~ vec (non-replicatingviral vector)
- repvec (Replicating viral Vector)
bac (bacterial vector)
Plasmid (Plasmid vector)

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INFIX
• to identify the viral vector type,
• e.g.:
• -adeno- adenovirus
• -cana- canarypox virus
• -foli- fowlpox virus
• -erpa- herpes virus
• -lenti- lentivirus
• -morbilli- Paramyxoviridae morbillivirus
• -parvo- adeno-associated virus
• -retro- other retrovirus
• -vaci- vaccinia virus
• -lis- Listeria monocytogenes

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• pexastimogene devacirepvec is a genetically
engineered vaccinia poxvirus expressing GM‐CSF
being developed as a broad spectrum anti-tumour
virus.

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• pexa~ prefix distinct name
• stimo~ Infix(stimulating factor)
• Gene ~ suffix
• SECOND WORD
• de ~ prefix
• vaci~ vaccinia (pox)
• repvec~ replicating virus

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RECENT ADVANCES
CHECKPOINT INHIBITORS

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• The PD-1/PD-L1 pathway represents an adaptive
immune resistance mechanism exerted by tumor
cells in response to endogenous immune anti-
tumor activity.
• PD-L1 is overexpressed on tumor cells or on non-
transformed cells in the tumor microenvironment.
PD-L1 expressed on the tumor cells binds to PD-1
receptors on the activated T cells, which leads to
the inhibition of the cytotoxic T cells.

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• PD-1 and PD-L1/PD-L2 belong to the family of
immune checkpoint proteins that act as co-
inhibitory factors that can halt or limit the
development of the T cell response.
• The PD-1/PD-L1 interaction ensures that the
immune system is activated only at the appropriate
time in order to minimize the possibility of chronic
autoimmune inflammation.

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• PD-1 inhibitors: These drugs are given by IV
(intravenously). Examples of drugs that target PD-1
include:
• Pembrolizumab (Keytruda)
• Nivolumab (Opdivo)
• Cemiplimab (Libtayo)

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• PD-L1 inhibitors: Examples of drugs that target PD-
L1 include:
• Atezolizumab (Tecentriq)
• Avelumab (Bavencio)
• Durvalumab (Imfinzi)

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USEDIN
• Nivolumab (Opdivo®) – FDA approval
• Melanoma – unresectable or metastatic; single
agent or combination with ipilimumab
• NSCLC – metastatic; with progression on or after
platinum-based chemotherapy and EGFR or ALK
therapy if EGFR or ALK positive
• Renal Cell – advanced disease who have received 1
or 2 prior therapies

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• Pembrolizumab (Keytruda®) – FDA approval
• Melanoma , NSCLC
• Shows promising activity in SCLC, esophageal,
breast, ovarian, head & neck, pancreatic,
lymphomas.

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SIDE EFFECTS
• Immune-mediated toxicity
• Occasional (5-20%)
• Fatigue
• Rash – maculopapular, pruritis
• Diarrhea/colitis – initiate steroids early, taper slowly
• Hepatitis/liver enzyme abnormalities
• Infusion reactions
• Endocrinopathies – thyroid, adrenal, hypophysitis
• Infrequent (<5%)
• Pneumonitis

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FUTURE ASPECTS IN
IMMUNOTHERAPY

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Vaccines
IMMUNO VACCINES that targets the HER2 receptor
which can be used in breast cancer
• CIMA VAX-EGF lung cancer vaccine developed in
Cuba

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PROTEOMICS
• Assessing various types of Proteins which are
expressed by various types of Cancer which can be
used for diagnosis is being under study.
• PROTEOMICS is under research for cancers like
ovary oral and lung cancers

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NEWER DRUGS
• IDH1 Inhibitors are being under study for solid
tumors like cholangiocarcinoma.

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Recently approved drugs
• CEMIPLIMAB a first check point inhibitors approved
for advanced BASAL CELL CARCINOMA on February
2021
• More recently on May 2021 FDA gave approval for
AMIVANTAMAB a bispecific antibody targets EGFR
and MET receptor used for Advanced or metastatic
NSCLC.

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THANK YOU