Articles by Alice
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Sutro Biopharma has just opened a study in non small cell lung cancer, investigating luvelta, an ADC targeted against FRalpha, which is over…
Sutro Biopharma has just opened a study in non small cell lung cancer, investigating luvelta, an ADC targeted against FRalpha, which is over…
Liked by Alice Yam
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It's great to work for a company where everyone can bring their true self to work! Thank you Vas Narasimhan for helping to enable a welcoming…
It's great to work for a company where everyone can bring their true self to work! Thank you Vas Narasimhan for helping to enable a welcoming…
Liked by Alice Yam
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Excited that our latest paper on immunogenicity risk assessment of knobs-into-holes bispecific antibodies was just published in mAbs!
Excited that our latest paper on immunogenicity risk assessment of knobs-into-holes bispecific antibodies was just published in mAbs!
Liked by Alice Yam
Publications
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RF1 attenuation enables efficient non-natural amino acid incorporation for production of homogeneous antibody drug conjugates
Science Reports
Amber codon suppression for the insertion of non-natural amino acids (nnAAs) is
limited by competition with release factor 1 (RF1). Here we describe the genome
engineering of a RF1 mutant strain that enhances suppression efficiency during
cell-free protein synthesis, without significantly impacting cell growth during
biomass production. Specifically, an out membrane protease (OmpT) cleavage site
was engineered into the switch loop of RF1, which enables its…Amber codon suppression for the insertion of non-natural amino acids (nnAAs) is
limited by competition with release factor 1 (RF1). Here we describe the genome
engineering of a RF1 mutant strain that enhances suppression efficiency during
cell-free protein synthesis, without significantly impacting cell growth during
biomass production. Specifically, an out membrane protease (OmpT) cleavage site
was engineered into the switch loop of RF1, which enables its conditional
inactivation during cell lysis. This facilitates extract production without
additional processing steps, resulting in a scaleable extract production process.
The RF1 mutant extract allows nnAA incorporation at previously intractable sites
of an IgG1 and at multiple sites in the same polypeptide chain. Conjugation of
cytotoxic agents to these nnAAs, yields homogeneous antibody drug conjugates
(ADCs) that can be optimized for conjugation site, drug to antibody ratio (DAR)
and linker-warheads designed for efficient tumor killing. This platform provides
the means to generate therapeutic ADCs inaccessible by other methods that are
efficient in their cytotoxin delivery to tumor with reduced dose-limiting
toxicities and thus have the potential for better clinical impact. -
Engineering toward a bacterial "endoplasmic reticulum" for the rapid expression of immunoglobulin proteins
Mabs
Antibodies are well-established as therapeutics, and the preclinical and clinical pipeline of these important biologics is growing rapidly. Consequently, there is considerable interest in technologies to engineer and manufacture them. Mammalian cell culture is commonly used for production because eukaryotic expression systems have evolved complex and efficient chaperone systems for the folding of antibodies. However, given the ease and manipulability of bacteria, antibody discovery efforts…
Antibodies are well-established as therapeutics, and the preclinical and clinical pipeline of these important biologics is growing rapidly. Consequently, there is considerable interest in technologies to engineer and manufacture them. Mammalian cell culture is commonly used for production because eukaryotic expression systems have evolved complex and efficient chaperone systems for the folding of antibodies. However, given the ease and manipulability of bacteria, antibody discovery efforts often employ bacterial expression systems despite their limitations in generating high titers of functional antibody. Open-Cell Free Synthesis (OCFS) is a coupled transcription-translation system that has the advantages of prokaryotic systems while achieving high titers of antibody expression. Due to the open nature of OCFS, it is easily modified by chemical or protein additives to improve the folding of select proteins. As such, we undertook a protein additive screen to identify chaperone proteins that improve the folding and assembly of trastuzumab in OCFS. From the screen, we identified the disulfide isomerase DsbC and the prolyl isomerase FkpA as important positive effectors of IgG folding. These periplasmic chaperones function synergistically for the folding and assembly of IgG, and, when present in sufficient quantities, gram per liter IgG titers can be produced. This technological advancement allows the rapid development and manufacturing of immunoglobulin proteins and pushes OCFS to the forefront of production technologies for biologics.
Other authorsSee publication -
Production of site-specific antibody-drug conjugates using optimized non-natural amino acids in a cell-free expression system
Bioconjugate Chemistry
Antibody-drug conjugates (ADCs) are a targeted chemotherapeutic currently at the cutting edge of oncology medicine. These hybrid molecules consist of a tumor antigen-specific antibody coupled to a chemotherapeutic small molecule. Through targeted delivery of potent cytotoxins, ADCs exhibit improved therapeutic index and enhanced efficacy relative to traditional chemotherapies and monoclonal antibody therapies. The currently FDA-approved ADCs, Kadcyla (Immunogen/Roche) and Adcetris (Seattle…
Antibody-drug conjugates (ADCs) are a targeted chemotherapeutic currently at the cutting edge of oncology medicine. These hybrid molecules consist of a tumor antigen-specific antibody coupled to a chemotherapeutic small molecule. Through targeted delivery of potent cytotoxins, ADCs exhibit improved therapeutic index and enhanced efficacy relative to traditional chemotherapies and monoclonal antibody therapies. The currently FDA-approved ADCs, Kadcyla (Immunogen/Roche) and Adcetris (Seattle Genetics), are produced by conjugation to surface-exposed lysines, or partial disulfide reduction and conjugation to free cysteines, respectively. These stochastic modes of conjugation lead to heterogeneous drug products with varied numbers of drugs conjugated across several possible sites. As a consequence, the field has limited understanding of the relationships between the site and extent of drug loading and ADC attributes such as efficacy, safety, pharmacokinetics, and immunogenicity. A robust platform for rapid production of ADCs with defined and uniform sites of drug conjugation would enable such studies. We have established a cell-free protein expression system for production of antibody drug conjugates through site-specific incorporation of the optimized non-natural amino acid, para-azidomethyl-l-phenylalanine (pAMF). By using our cell-free protein synthesis platform to directly screen a library of aaRS variants, we have discovered a novel variant of the Methanococcus jannaschii tyrosyl tRNA synthetase (TyrRS), with a high activity and specificity toward pAMF. We demonstrate that site-specific incorporation of pAMF facilitates near complete conjugation of a DBCO-PEG-monomethyl auristatin (DBCO-PEG-MMAF) drug to the tumor-specific, Her2-binding IgG Trastuzumab using strain-promoted azide-alkyne cycloaddition (SPAAC) copper-free click chemistry. The resultant ADCs proved highly potent in in vitro cell cytotoxicity assays.
Other authorsSee publication -
The octarepeat region of the prion protein is conformationally altered in PrP(Sc)
PLoS ONE
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Characterization of prion protein (PrP)-derived peptides that discriminate full-length PrPSc from PrPC
PNAS
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Hsp110 cooperates with different cytosolic HSP70 systems in a pathway for de novo folding
J Biol Chem
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Chinese
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Spanish
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More activity by Alice
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Join us in welcoming Sherwin C. as our new Chief Legal Officer and Corporate Secretary! Read more about new team members here:…
Join us in welcoming Sherwin C. as our new Chief Legal Officer and Corporate Secretary! Read more about new team members here:…
Liked by Alice Yam
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I'm thrilled to congratulate the incredible team behind the groundbreaking discovery of this first-in-class A2A receptor antibody! If you have any…
I'm thrilled to congratulate the incredible team behind the groundbreaking discovery of this first-in-class A2A receptor antibody! If you have any…
Liked by Alice Yam
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Absolutely thrilled about the potential of integrating a ROR1 exactecan ADC into our pipeline! Exciting prospects ahead with its best in class…
Absolutely thrilled about the potential of integrating a ROR1 exactecan ADC into our pipeline! Exciting prospects ahead with its best in class…
Liked by Alice Yam
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Bill Newell, CEO, Sutro Biopharma, recently joined Brad Loncar, Founder, BiotechTV, for an insightful conversation. They delved into Sutro's recent…
Bill Newell, CEO, Sutro Biopharma, recently joined Brad Loncar, Founder, BiotechTV, for an insightful conversation. They delved into Sutro's recent…
Liked by Alice Yam
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Ipsen announces exclusive global licensing agreement with Sutro for an ADC targeting solid tumors. For more info, https://lnkd.in/gs5WADqi #Ipsen…
Ipsen announces exclusive global licensing agreement with Sutro for an ADC targeting solid tumors. For more info, https://lnkd.in/gs5WADqi #Ipsen…
Liked by Alice Yam
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In business news, Ipsen and Sutro Biopharma announced an exclusive global licensing agreement for STRO-003. STRO-003, an antibody-drug conjugate…
In business news, Ipsen and Sutro Biopharma announced an exclusive global licensing agreement for STRO-003. STRO-003, an antibody-drug conjugate…
Liked by Alice Yam
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Thrilled to announce the exclusive global licensing agreement between Ipsen and Sutro Biopharma, targeting solid tumors with a fantastic ADC program,…
Thrilled to announce the exclusive global licensing agreement between Ipsen and Sutro Biopharma, targeting solid tumors with a fantastic ADC program,…
Liked by Alice Yam
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Sutro’s ROR1 targeting ADC, STRO-003 demonstrates immune-modulating properties that may enhance checkpoint blockade American Association for Cancer…
Sutro’s ROR1 targeting ADC, STRO-003 demonstrates immune-modulating properties that may enhance checkpoint blockade American Association for Cancer…
Liked by Alice Yam
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Thrilled to see this news! Congratulations to both Ipsen and Sutro teams for their collaborative approach and the dedication of the BD teams Nick…
Thrilled to see this news! Congratulations to both Ipsen and Sutro teams for their collaborative approach and the dedication of the BD teams Nick…
Liked by Alice Yam
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Thrilled to have had Bhairav Parekh, Senior Director of Regulatory CMC, share his expertise with the students of University of California, Berkeley's…
Thrilled to have had Bhairav Parekh, Senior Director of Regulatory CMC, share his expertise with the students of University of California, Berkeley's…
Liked by Alice Yam
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I'm excited to be speaking this year at the 20th Annual PEGS Boston conference from May 13th-17th. Hope to see you there! https://www.pegsummit.com/…
I'm excited to be speaking this year at the 20th Annual PEGS Boston conference from May 13th-17th. Hope to see you there! https://www.pegsummit.com/…
Liked by Alice Yam
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Hans-Peter Gerber, Ph.D., Chief Scientific Officer presented at the 14th Annual World Antibody Drug Conjugates London 2024. Click the link for more…
Hans-Peter Gerber, Ph.D., Chief Scientific Officer presented at the 14th Annual World Antibody Drug Conjugates London 2024. Click the link for more…
Liked by Alice Yam
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I am very excited to be presenting at the inaugural Alpha-Twists and Beta-Turns of recombinant protein production meeting on Mar-21 at the Frederick…
I am very excited to be presenting at the inaugural Alpha-Twists and Beta-Turns of recombinant protein production meeting on Mar-21 at the Frederick…
Liked by Alice Yam
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