• Source: ImmunoGen

ImmunoGen, Inc. was a biotechnology company focused on the development of antibody-drug conjugate (ADC) therapeutics for the treatment of cancer. ImmunoGen was founded in 1981 and was headquartered in Waltham, Massachusetts.
An ImmunoGen ADC contains a manufactured antibody that binds to a target found on cancer cells, with one of the company's potent cell-killing agents attached as a "payload". The antibody serves to deliver the cell-killing agent specifically to cancer cells bearing its target and the payload serves to kill these cells. In some cases, the antibody also has anticancer activity.
In November 2023, AbbVie, an American pharmaceutical company, announced it was buying ImmunoGen for $10.1 billion.




Linkage technology


Currently approved ADCs with ImmunoGen technology employ one of the company's maytansinoid cell-killing agents, either DM1 or DM4, or one of the company's DNA-acting IGN payloads.

DM1 attached to an antibody with ImmunoGen's thioether linker is called "emtansine" in its INN name
trastuzumab emtansine, marketed as Kadcyla
DM1 attached to an antibody with ImmunoGen's SPP linker is called "mertansine".
DM4 attached with ImmunoGen's SPDB linker is called "ravtansine"
indatuximab ravtansine (BT062) targeting multiple myeloma,
anetumab ravtansine (BAY94-9343) targeting mesothelin (to treat mesothelioma), starting phase II trial in 2016
coltuximab ravtansine (SAR3419) targeting CD19 to treat acute lymphoblastic leukemia (ALL).
DM4 attached with ImmunoGen's sSPDB linker is called "soravtansine"
mirvetuximab soravtansine
ImmunoGen also developed isatuximab, a monoclonal antibody without linkage to a toxin.




Pipeline


ImmunoGen uses its ADC technology to develop its own product candidates. The mirvetuximab, which has been submitted for FDA approval, is being developed as a monotherapy or a standalone treatment for ovarian cancer. Other products currently in clinical-stage development include:

IMGN853, (mirvetuximab soravtansine) targeting FRα, and using DM4.
IMGN529, targeting CD37 for Non-Hodgkin lymphoma (NHL).
IMGN289, targeting EGFR
IMGN779, a CD33-Targeted Antibody-Drug Conjugate (ADC) with a new DNA-Alkylating agent acts on AML Cells.
IMGN632, anti-CD123
SAR408701 in collaboration with Sanofi
SAR428926 in collaboration with Sanofi
SAR566658 in collaboration with Sanofi
SAR650984 in collaboration with Sanofi
LY3076226 in collaboration with Eli Lilly
PCA062 in collaboration with Novartis
an undisclosed antibody in collaboration with Amgen




Collaborations & licensing


The company also selectively out licenses limited use of its technology to other companies. Companies licensing ImmunoGen's technology include Amgen, Bayer HealthCare, Biotest, Genentech/Roche, Eli Lilly, Novartis, Sanofi, and Takeda. Roche's Kadcyla (ado-trastuzumab emtansine) utilizes ImmunoGen's ADC technology. It has been approved and launched in a number of countries, including the US, where it is marketed by Genentech, a member of the Roche Group. In October 2015, the company disclosed that Kadcyla had failed to meet its primary endpoint in the Phase II/III GATSBY trial investigating the second line treatment of HER2-positive advanced gastric cancer.




References






External links


Official website
• Source: Immunogen

An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism. Immunogens that generate antibodies are called antigens ("antibody-generating"). Immunogens that generate antibodies are directly bound by host antibodies and lead to the selective expansion of antigen-specific B-cells. Immunogens that generate T-cells are indirectly bound by host T-cells after processing and presentation by host antigen-presenting cells.
An immunogen can be defined as a complete antigen which is composed of the macromolecular carrier and epitopes (determinants) that can induce immune response.
An explicit example is a hapten. Haptens are low-molecular-weight compounds that may be bound by antibodies, but cannot elicit an immune response. Consequently, the haptens themselves are nonimmunogenic and they cannot evoke an immune response until they bind with a larger carrier immunogenic molecule. The hapten-carrier complex, unlike free hapten, can act as an immunogen and can induce an immune response.
Until 1959, the terms immunogen and antigen were not distinguished.




Used carrier proteins


Keyhole limpet hemocyanin
It is copper-containing respiratory protein, isolated from keyhole limpets (Megathura crenulata). Because of its evolutionary distance from mammals, high molecular weight and complex structure it is usually immunogenic in vertebrate animals.
Concholepas concholepas hemocyanin
(also blue carrier immunogenic orotein) It is alternative to KLH isolated from Concholepas concholepas. It has the similar immunogenic properties as KLH but better solubility and therefore better flexibility.
Bovine serum albumin
It is from the blood sera of cows and has similarly immunogenic properties as KLH or CCH. The cationized form of BSA (cBSA) is highly positively charged protein with significantly increased immunogenicity. This change possesses a greater number of possible conjugated antigens to the protein.
Ovalbumin
Also known as egg albumin, OVA is the main protein (60-75%) found in hen egg white. OVA is soluble in dimethyl sulfoxide (DMSO), which enables the conjugation of haptens that are not soluble in aqueous buffers. The immune response can be enhanced using an adjuvant injected together with the immunogen.




Immunological adjuvants


An adjuvant (from Latin adiuvare – to help) is any substance, distinct from antigen, which enhances immune response by various mechanisms: recruiting of professional antigen-presenting cells (APCs) to the site of antigen exposure; increasing the delivery of antigens by delayed/slow release (depot generation); immunomodulation by cytokine production (selection of Th1 or Th2 response); inducing T-cell response (prolonged exposure of peptide-MHC complexes [signal 1] and stimulation of expression of T-cell-activating co-stimulators [signal 2] on the APCs' surface) and targeting (e. g. carbohydrate adjuvants which target lectin receptors on APCs). Adjuvants have been used as additives to improve vaccine efficiency since the 1920s. Generally, administration of adjuvants is used both in experimental immunology and in clinical settings to ensure a high quality/quantity memory-enhanced antibody response, where antigens must be prepared and delivered in a fashion that maximizes production of a specific immune response. Among commonly used adjuvants are complete and incomplete Freund's adjuvant and solutions of aluminum hydroxide or aluminum phosphate.




References

Kata Kunci Pencarian:

• Vaksinasi
• Indeks Bioteknologi NASDAQ
• ImmunoGen
• Immunogen
• AbbVie
• Viral envelope
• Mertansine
• Antigen
• DNA vaccine
• Cross-reactivity
• Immunization
• Cantilever