Immunopharmacology
Subclass, Drug Mechanism of Action Effects Clinical Applications P, T, I
Immunosuppressive Immunologic effects due to Suppressive effects Autoimmune disorders Pseudomotor cerebri, fever,
Agents: their ability to modify inflammatory cytokines, Modulate allergic reactions myalgias, arthralgias,
cellular functions rather chemokines, and other (asthma) malaise
than to direct cytotoxicity mediators of inflammation Organ transplantation
Anti-inflammatory and
Glucocorticoids immunosuppressive action
Calcineurin Inhibitors: Binds to cyclophillin > Blocks T-cell activation Immunosuppressive agent Nephrotoxicity,
inhibits calcineurin activity > Most commonly used Sole immunosuppressant for hypertension, Kaposi
inhibits T-cell specific immunosuppressant for cadaveric transplantation of sarcoma, hyperglycemia
Cyclosporine transcription factor (NF-AT) renal transplantation kidneys etc.
activation > inhibits gene #1 renal transplant
(CSA, Cyclosporin A) transcription of IL-2, IL-3,
IFN-y
Binds to immmunophilin FK- Immunosuppressant Liver and kidney and stem Nephrotoxicity,
binding protein > inhibits macrolide antibiotic (Strep. cell transplantation neurotoxicity, hyperglycemia
Tacrolimus calcineurin > inhibits T-cell tsukubaensis) Atopy, psoriasis *HUS (tacrolimus +
specific transcription factor Liver, kidney, stem cell sirolimus)
(FK 506) (NF-AT) activation transplant
mTor Inhibitor: Immunosuppressant Binds to immunophilin Psoriasis Profound myelosuppression,
macrolide antibiotic (Strep. FK506 binding protein 12 > Uveoretinitis hepatotoxicity
hygroscopicus) inhibits kinase activity of Suppresses hematopoietic
Potent inhibitor of beta-cell mTor recovery after myelotoxic
proliferation and Ig Inhibits mononuclear cell treatment
Sirolimus production proliferation response to CSF Prevent rejection of solid
st
[Rapamycin] 1 immunosuppressant in organ allografts
both solid organ and stem
cell transplantation
Eluting coronary stents
Derivative of sirolimus for Used solid organ transplant
cardiac transplants recipients
Everolimus Rapalog with better
[Rapalog] bioavailability than sirolimus
1
Immunosuppressant (Ca)
Temsirolimus
[Rapalog]
st
1 line agent for chronic Inhibits a series of T and B Refractory rejection in solid GI disturbances, headache,
allograft vasculopathy in lymphocyte responses > by and hematopoietic stem cell hypertension, reversible
Mycophenolate cardiac transplants initiation of de novo transplant myelosuppression (primary
Semisynthetic derivative of synthesis of purine Prophylaxis/tx to prevent neutropenia)
Mofetil (MMF) mycophenoloc acid: graft-vs-host disease in
Penicillium glaucus hematopoietic stem cell
transplantation
Immunomodulatory Multiple myeloma (initial dx Teratogenicity, peripheral
Derivatives of Thalidomide and relapse-refractory neuropathy, rash, fatigue,
disease) hypothyroidism, increased
(IMiDs): Myelodysplastic syndrome risk of DVT > warfarin
Thalidomide AML
Erythema nodosum
leprosum
Myelodysplastice syndrome
Lenolidomide with the chromosome 5q31
Less toxicity
Investigated for
Pomalidomide myelodysplasia, multiple
(CC-4047) myeloma
Cytotoxic Agents: Metabolized to 6- Antimetabolite Renal allograft Bone marrow suppression,
mercaptopurines (prodrug) AGN highly teratogenic, GI
Inhibits purine synthesis > SLE disturbances, skin rashes,
Azathioprine interferes with NA drug fever, hepatic
metabolism > inhibits dysfunction
lymphoid cell proliferation > Drug interaction: use of
inhibits cellular and humoral allopurinol
responses
Alkylating agent Destroys proliferation Smaller doses: autoimmune Pancytopenia, hemorrhagic
Most efficacious lymphoid and alkylate DNA disorders including SLE and cystitis, electrolyte
Cyclophosphamide immunosuppressive drug and other molecules in Wegener’s granulomatosis disturbances
resting cells
Prodrug of an inhibitor of RA Teratology
Leflunomide pyrimidine synthesis
Inhibits lymphoid cells
2
Appears to have antiviral
activity
Antimalarial agent with Autoimmune disorders
immunosuppressant Tx and prevention of graft-
activities vs-host disease after
Increase pH of lysosomal allogeneic stem cell
and endosomal transplantation
Hydroxychloroquine compartments > suppress
intracellular antigen
processing and loading of
peptides onto MHC class 2
molecules > decrease T-cell
activation
ITP refractory to prednisone
Vincristine
Prevents mast cell
degranulation > prevents
Vinblastine release of histamine and
other vasoactive
agents/compounds
RA, graft-vs-host disease Oral
Methotrexate idiosyncratic reactions to
purine antagonists
Cytarabine
Antibiotic
Used at the time of
Dactinomycin impending renal transplant
rejection
Adenosine deaminase Pre-op regimen prior to Preoperative regimen prior
inhibitor transplant to transplants to provide
Pentostatin Antineoplastic agent for severe immunosuppression
lymphoid malignancies > to prevent allograft rejection
profound lymphopenia
Immunosuppressive Antiserum is obtained by
Antibodies: immunization of horses,
sheep or rabbits with human
Antilymphocyte and lymphoid cells
3
Antithymocyte
Antibodies
CD3 molecule on surface of Blocks killing by cytotoxic More effective in reversing
human thymocytes human T-cells and other T- acute rejection
Muromonab Mature T-cells cell functions Tx of renal allograft rejection
crises and steroid-resistant
(CD3) acute cardiac and hepatic
transplant rejection
Polyclonal human Ig Reduction of T helper cells Kawasaki disease
Prepared for pools of Increase of suppresses T- SLE and refractory ITP
thousands of healthy donors cells
with no specific antigen Decreased spontaneous Ig
Immune Globulin target production
Intravenous (IGIV) Fc receptor blockade
Idiotypic-anti-idiotypic
interactions with pathologic
Abs
Prevention of Rh hemolytic
Rho (D) Immune disease of the newborn
Globulin Microdose
Made from pools of selected
human or animal donors
Hyperimmune with high titers of antibodies
against particular agents of
Immunoglobulins interest such as viruses or
toxins
Monoclonal Antibodies: Humanized IgG with a kappa Tx of B-cell chronic Lymphopenia, neutropenia,
Antitumor MABs: chain > binds to CD52 found lymphocytic leukemia > anemia, thrombocytopenia
on normal and malignant B patients treated with
and T lymphocytes, NK cells, alkylating agents and failed
monocytes fludarabine tx
Alemtuzumab Depletes leukemic and
normal cells by direct
antibody-dependent lysis
st
Binds to vascular endothelial Antiangiogenic drug > inhibit 1 -line tx of metastatic Hemorrhage, GI perforation,
growth factor (VEGF) and growth of blood vessels in colorectal ca, alone or with wound healing problems
4
inhibits its binding to tumors 5-FU
receptor on endothelial cells Non-small cell lung ca
Bevacizumab Humanized IgG1 MAB
Human-mouse chimeric Tx of metastatic colorectal Generation of HAMAs
monoclonal Ab ca that overexpresses EGFR (human-mouse antibody) –
Cetuximab May be administered with 4%
irinotecan
Humanized IgG monoclonal Tx of CD33 AML > patients Severe myelosuppression
antibody with kappa light 60 years old and older in especially neutropenia (with
Gemtuzumab chain specific for CD33 first relapse ozogamicin), significant
Coupled with ozogamicin hepatotoxicity,
hypersensitivity reaction
Human IgG1 monoclonal Ab Binds to all B-cells > lyze B- Chronic lymphocytic
directed against CD20 CLL cells in the presence of leukemia refractory to
Ofatumumab Risk: hep B virus reactivation complement and mediate fludrabine and alemtuzumab
Ab-dependent cellular
toxicity
Fully human IgG2 kappa light Binds with EGFR > inhibiting Tx of EGFR-expressing Do not elicit HAMAs
Panitumumab chain MAB EGFR from binding metastatic colorectal ca with
disease profression
Chimeric murine-human Binds to CD20 molecule on Relapsed or refractory low-
monoclonal IgG1 (human Fc) normal and malignant B grade or follicular B-cell non-
Complement-mediated lysis lymphocytes Hodgkin’s lymphoma
antibody-dependent cellular
Rituximab cytotoxicity induction of
apoptosis
Recombinant DNA-derived HER2/neu positive breast ca
humanized monoclonal and patients with metastatic
Trastuzumab antibody gastric or gastroesophageal
junction adenocarcinoma
MABs Used to Deliver Murine F(ab)2 fragment CEA is upregulated in Used for imaging metastatic
Isotopes to Tumors: from an anti- patients with GI carcinoma colorectal ca to determine
carcinoembryonic antigen extent of disease
Arcitumumab (CEA) antibody labeled with (immunoscintigraphy)
Tc
Murine monoclonal
antibody specific for
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prostate specific membrane
antigen
Capromab- Used in immunoscintigraphy
of patients with prostate ca
pendetide and postprostatectomy
patients with rising PSAB
level to determine extent
An anti-CD20 murine Used for patients with
monoclonal antibody relapsed or refractory low-
Ibritumomab- labeled with isotropic grade, follicular, or B-cell
yttrium (y) or in radiation of non-Hodgkin’s lymphoma
tiuxetan isotope provides the major Patients with rituximab-
antitumor activity refractory follicular disease
Diagnostic purposes to A mouse monoclonal
determine extent of disease antibody coupled to Tc
Nofetumomab and to stage patients with Accurate indicator of extent
small cell lung ca of biopsy
Binds to 40Kd Ag
Anti-CD20 monoclonal Patients with CD20-positive Contraindicated in patients Severe cytopenia
antibody and complexed follicular non-Hodgkin’s with > 25% BM involvement
Tositumomab with iodine 131 (I) lymphoma refractory to
rituximab and standard Tp
MABs Used as A completely human IgG1 Blocks the interaction of
Immunosuppressants Anti- approved for use in RA TNF-alpha with receptors
juvenile idiopathic arthritis but do not bind TNF-beta;
Inflammatory Agents: lyzes cells expressing TNF-
Anti-TNF-alpha MABs: alpha
Adalimumab
Recombinant humanized Neutralizes the activity of Crohn’s disease and RA
Fab fragment that binds to membrane-associated and
Certolizumabpegol TNF-alpha soluble TNF-alpha without
Coupled with 40-kDa lysing cells
polyethylene glycol
Shortest half-life Dimeric fusion human IgG1 RA
Etanercept Binds to both TNF-alpha and constant region fused on Alkylating spondylitis
TNF-beta TNF receptor
6
Human IgG monoclonal Ab RA, ankylosing spondylitis,
Binds to soluble and psoriatic arthritis
Golimumab membrane-associated TNF-
alpha but does not lyze cells
Human-mouse chimeric IgG1 Crohn’s disease, ulcerative
MAB colitis, RA, ankylosing
Infliximab Possesses human constant spondylitis, psoriatic
(Fc) region and murine arthritis, plaque psoriasis
variable region
Recombinant fusion protein Binds more tightly to RA, JIA Latent TB reactivation
CH2 and CH3 domains of CD80/86 than CD28; blocks
Abatacept human IgG activation of T-cells by
Deliver an inhibitory signal binding to CD80/86
to T-cells
Consists of CD2-binding Inhibits activation of T-cells Tx of plaque psoriasis Monitor peripheral T-cell
protion of leukocyte- by binding to cell surface counts (CD4 <250 cells/uL)
Alefacept function-associated antigen- CD2
3 (LFA-3) fused to human
IgG1 Fc region
Chimeric-mouse human IgG1 Binds to CD25, the IL-2 Prophylaxis: acute organ
Basiliximab receptor alpha chain on transplantation
activated lymphocytes
Humanized IgG1 Same Same?
Daclizumab
Recombinant humanized Tx of adult patients with
Efalizumab anti-CD11 a MAB severe psoriasis
Humanized IgG4 monoclonal MS, CD (with inadequate
antibody that binds to the a4 response to conventional
Natalizumab subunit of a4b1 and a4b7 treatment)
Allergic asthma in adults and Anti-IgE humanized MAB Elevation of serum IgE level
Omalizumab adolescent refractory to > 1 year after administration
inhaled corticosteroids
Recombinant humanized RA (refractory to other anti- Risk of infection
IgG1 that binds to soluble TNF alpha biologicals)
Tocilizumab and membrane-associated Used in combination with
IL-6 receptors > methotrexate or other
DMARDs
7
Human IgG1 monoclonal Ab Mild to severe plaque
Binds with the p40 subunit psoriasis
Ustekinumab of IL-12 and IL-23 cytokines > Faster and longer term
improvement with
infrequent dosing
Other MABs: Fab fragment of murine-
human MAB
Inhibits fibrinogen, von
Abciximab Willebrand factor, adhesion
molecules from binding to
platelets > prevent
aggregation
Human IgG2 monoclonal Ab Post-menopausal Hypocalcemia
Denosumab specific for RANKL osteoporosis
Humanized IgG MAB that Paroxysmal nocturnal Risk of meningococcal
Eculizumab binds C5 complement hemoglobinuria, reducing infection
component for RBC transfusion
Binds to fusion protein of Used in neonates in
RSV > prevent infection in reduction in frequency and
Palivizumab susceptible cells in the hospitalizations (50%)
airways
Recombinant human IgG Fab Prevents new blood vessel Intravitreal injection
that binds to VEGF-alpha formation by blocking VEGF (macular degeneration)
Ranibizumab from binding to its receptor Pegaptinib – pegylated
oligonucleotide that binds
extracellular VEGF; given
intravitreal to sloq MD
Cytokine Inhibitors: Recombinant form of RA
naturally occurring IL-1
Anakinra receptor anatagonist
Recombinant human anti-IL-
Canakinumab 1B MAB
Dimeric fusion protein: IL-
1RI and IL-1 receptor
Rilonacept accessory protein (IL-1RAcP)
fused to the Fc portion of
human IgG1
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