Illinois State Police said six people were in a vehicle in the northbound lanes of I-57 near 111th Street when shots were fired at about 10:30 p.m.
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Police said a 19-year-old man, a 1-year-old girl and a 14-year-old boy were pronounced dead at the scene.
The Cook County Medical Examiner's Office identified the victims as 1-year-old A-mara Hall, 13-year-old William L. Smith and 19-year-old Nasir Hall.
A woman was transported to the University of Chicago Medical Center in serious but stable condition, police said. Two boys, ages 13 and 14, were transported to Comer Children's Hospital in serious but stable condition, police said.
The female driver of the SUV was able to get off of I-57 at 111th Street and Hamlet Avenue. The vehicle was riddled with bullets. All northbound lanes of I-57 from 127th to 111th Street were closed, but reopened at 4:22 a.m., police said.
Crisis responder Andrew Holmes and community activists are offering a $7,000 reward for information leading to an arrest.
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"It's clear as day," Holmes said. "You can see right through the vehicle. You seen the children in there. You seen the people in there. I mean come on, just simply turn yourself in because I'll tell you this much, there's technology on the expressway."
Holmes expressed his outraged over the violence.
"What if somebody did the same thing to you? Come by and do a drive-by on you? How would you feel? How would your mother feel? How would your grandmother feel? This is a baby. This is a child. And if anybody knows this is your relative that drove up and took this baby's life, think about your own baby," Holmes said.
Local pastor and victim advocate Donovan Price responded to a very chaotic hospital scene overnight.
"Heartbreaking on so many levels. Chaotic and trying to get information. Things like the mom trying to get information. Could you imagine trying to get information on your child's death?" Price said.
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Price has spent much of the day consoling an inconsolable mother, who lost her 13-year-old son.
"Pure shock, and how are they going to make it through this thing that they've seen so much on TV and never thought they would experience themselves? From going to identify the body, to now planning vigils and funerals. The kids should be going back to school tomorrow," Price said.
Dr. Sharon Pughsley, who lost her daughter to gun violence, also spoke out.
"My heart aches for the family who's going through this," Pughsley said. "It hurts me just to hear each day when somebody's life is taken in a horrific manner. These kids did not deserve it."
Meanwhile, state police have not released any description of a suspect or a vehicle. There is also no word on what led up to the shooting.