13 b i o n t e c h i m n a t u r e m a g a z i n B rad Kremer had waited months to receive an experimental cancer vaccine called BNT122 during which time the melanoma on his skin had spread to his liver and spine His back pain was getting worse he was rapidly losing weight and new cancerous lesions kept appearing on his left thigh It was very scary says Kremer a 52 year old sales representative from Acton Massachusetts But within weeks of his first injection in March Kremer could see that the vaccine was working The coin sized melanoma spots that popped up from his skin were now flat discolourations measuring millimetres across I was actually witnessing the cancer cells shrinking before my eyes he says Several doses later his appetite has returned his back pain has subsided and scans show that his cancer is continuing to retreat Kremer s dramatic response exemplifies the medical potential of vac cines built on messenger RNA In this method strings of lab synthesized nucleotides train the immune system to recognize and destroy disease causing agents be they cancer cells or infectious viruses Other ways of making vaccines can achieve the same therapeutic objective But the potency versatility speed of manufacturing and low cost of mRNA make it an attractive platform for the rapid development and large scale production of new or custom made vaccines Early clinical results have demonstrated the technology s promise Researchers at BioNTech in Mainz Germany the manufacturer of the cancer vaccine that Kremer is receiving reported in 2017 that all of the first 13 people with advanced stage melanoma to receive the person alized immunotherapy which is tailor made to match the genetic profile of each person s cancer showed elevated immunity against the mutated bits of their tumours As a result these patients risk of developing new metastatic lesions was significantly reduced1 For viral diseases prophylactic vaccine candidates against rabies2 and pandemic influenza3 have each proved safe and induced protective antibody responses in healthy volunteers In both cases however the antiviral effects waned after less than a year suggesting that improvements are needed to provide more robust and long lasting immunity There s a lot of potential here says John Mascola director of the Vaccine Research Center at the US National Institutes of Health in Bethesda Maryland It s still early in the development of these vaccines but the platform has shown proof of concept MADE TO MEASURE Moderna Therapeutics is racing to develop mRNA vaccines further In 2018 company executives cut the ribbon on a US 130 million two storey football pitch sized manufacturing plant in Norwood Massachusetts about one hour s drive from the company s headquar ters in Cambridge Technicians at the new site synthesize and formulate mRNA for all of Moderna s early stage clinical trials including for an ongoing investigation of mRNA 4157 a personalized cancer vaccine that like BioNTech s BNT122 has shown preliminary signs of anti tumour activity in people with cancer Along with other companies testing the same strategy Moderna starts the process of making its personalized treatment by taking a pair of genetic profiles from each individual one from a biopsy of the tumour the other from a vial of healthy blood cells Algorithms K AT YE M AR TE N S B R IE R S 1 0 N A T U R E V O L 5 7 4 1 7 O C T O B E R 2 0 1 9 RNA THERAPIESOUTLOOK INJECTION OF HOPE Messenger RNA could help to boost immunity against cancer influenza and much more BY E L I E D O LG I N Brad Kremer received an experimental vaccine for his cancer 2019 Spri nger Nature Li mited All ri ghts reserved 2019 Spri nger Nature Li mited All ri ghts reserved rad Kremer had waited months to receive an experimental cancer vaccine called BNT122 during which time the melanoma on his skin had spread to his liver and spine His back pain was getting worse he was rapidly losing weight and new cancerous lesions kept appearing on his left thigh It was very scary says Kremer a 52 year old sales representative from Acton Massachusetts But within weeks of his first injection in March Kremer could see that the vaccine was working The coin sized melanoma spots that popped up from his skin were now flat discolourations measuring millimetres across I was actually witnessing the cancer cells shrinking before my eyes he says Several doses later his appetite has returned his back pain has subsided and scans show that his cancer is continuing to retreat Kremer s dramatic response exemplifies the medical potential of vac cines built on messenger RNA In this method strings of lab synthesized nucleotides train the immune system to recognize and destroy disease causing agents be they cancer cells or infectious viruses Other ways of making vaccines can achieve the same therapeutic objective But the potency versatility speed of manufacturing and low cost of mRNA make it an attractive platform for the rapid development and large scale production of new or custom made vaccines Early clinical results have demonstrated the technology s promise Researchers at BioNTech in Mainz Germany the manufacturer of the cancer vaccine that Kremer is receiving reported in 2017 that all of the first 13 people with advanced stage melanoma to receive the person alized immunotherapy which is tailor made to match the genetic profile of each person s cancer showed elevated immunity against the mutated bits of their tumours As a result these patients risk of developing new metastatic lesions was significantly reduced1 For viral diseases prophylactic vaccine candidates against rabies2 and pandemic influenza3 have each proved safe and induced protective antibody responses in healthy volunteers In both cases however the antiviral effects waned after less than a year suggesting that improvements are needed to provide more robust and long lasting immunity There s a lot of potential here says John Mascola director of the Vaccine Research Center at the US National Institutes of Health in Bethesda Maryland It s still early in the development of these vaccines but the platform has shown proof of concept MADE TO MEASURE Moderna Therapeutics is racing to develop mRNA vaccines further In 2018 company executives cut the ribbon on a US 130 million two storey football pitch sized manufacturing plant in Norwood Massachusetts about one hour s drive from the company s headquar ters in Cambridge Technicians at the new site synthesize and formulate mRNA for all of Moderna s early stage clinical trials including for an ongoing investigation of mRNA 4157 a personalized cancer vaccine that like BioNTech s BNT122 has shown preliminary signs of anti tumour activity in people with cancer Along with other companies testing the same strategy Moderna starts the process of making its personalized treatment by taking a pair of genetic profiles from each individual one from a biopsy of the tumour the other from a vial of healthy blood cells Algorithms K AT YE M AR TE N S B R IE R S 1 0 N A T U R E V O L 5 7 4 1 7 O C T O B E R 2 0 1 9 RNA THERAPIESOUTLOOK INJECTION OF HOPE Messenger RNA could help to boost immunity against cancer influenza and much more BY E L I E D O LG I N Brad Kremer received an experimental vaccine for his cancer 2019 Spri nger Nature Li mited All ri ghts reserved 2019 Spri nger Nature Li mited All ri ghts reserved

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